Comparing transmission potential networks based on social network surveys, close contacts and environmental overlap in rural Madagascar.

Social and spatial network analysis is an important approach for investigating infectious disease transmission, especially for pathogens transmitted directly between individuals or via environmental reservoirs. Given the diversity of ways to construct networks, however, it remains unclear how well networks constructed from different data types effectively capture transmission potential. We used empirical networks from a population in rural Madagascar to compare social network survey and spatial data-based networks of the same individuals. Close contact and environmental pathogen transmission pathways were modelled with the spatial data. We found that naming social partners during the surveys predicted higher close-contact rates and the proportion of environmental overlap on the spatial data-based networks. The spatial networks captured many strong and weak connections that were missed using social network surveys alone. Across networks, we found weak correlations among centrality measures (a proxy for superspreading potential). We conclude that social network surveys provide important scaffolding for understanding disease transmission pathways but miss contact-specific heterogeneities revealed by spatial data. Our analyses also highlight that the superspreading potential of individuals may vary across transmission modes. We provide detailed methods to construct networks for close-contact transmission pathogens when not all individuals simultaneously wear GPS trackers.

Food insecurity related to agricultural practices and household characteristics in rural communities of northeast Madagascar.

Ending hunger and alleviating poverty are key goals for a sustainable future. Food security is a constant challenge for agrarian communities in low-income countries, especially in Madagascar. We investigated agricultural practices, household characteristics, and food security in northeast Madagascar. We tested whether agricultural practices, demographics, and socioeconomics in rural populations were related to food security. Over 70% of respondents reported times during the last three years during which food for the household was insufficient, and the most frequently reported cause was small land size (57%). The probability of food insecurity decreased with increasing vanilla yield, rice yield, and land size. There was an interaction effect between land size and household size; larger families with smaller land holdings had higher food insecurity, while larger families with larger land had lower food insecurity. Other socioeconomic and agricultural variables were not significantly related to food insecurity, including material wealth, education, crop diversity, and livestock ownership. Our results highlight the high levels of food insecurity in these communities and point to interventions that would alleviate food stress. In particular, because current crop and livestock diversity were low, agricultural diversification could improve outputs and mitigate food insecurity. Development of sustainable agricultural intensification, including improving rice and vanilla cultivation to raise yields on small land areas, would likely have positive impacts on food security and alleviating poverty. Increasing market access and off-farm income, as well as improving policies related to land tenure could also play valuable roles in mitigating challenges in food security. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12571-021-01179-3.

Process Evaluation of a Community-Based Microbial Larviciding Intervention for Malaria Control in Rural Tanzania.

Microbial larviciding can be an effective component of integrated vector management malaria control schemes, although it is not commonly implemented. Moreover, quality control and evaluation of intervention activities are essential to evaluate the potential of community-based larviciding interventions. We conducted a process evaluation of a larval source management intervention in rural Tanzania where local staff were employed to apply microbial larvicide to mosquito breeding habitats with the aim of long-term reductions in malaria transmission. We developed a logic model to guide the process evaluation and then established quantitative indicators to measure intervention success. Quantitative analysis of intervention reach, exposure, and fidelity was performed to assess larvicide application, and interviews with larviciding staff were reviewed to provide context to quantitative results. Results indicate that the intervention was successful in terms of reach, as staff applied microbial larvicide at 80% of identified mosquito breeding habitats. However, the dosage of larvicide applied was sufficient to ensure larval elimination at only 26% of sites, which does not meet the standard set for intervention fidelity. We propose that insufficient training and protocol adaptation, environment and resource issues, and human error contributed to low larvicide application rates. This demonstrates how several small, context-specific details in sum can result in meaningful differences between intervention blueprint and execution. These findings may serve the design of other larval source management interventions by demonstrating the value of additional training, supervision, and measurement and evaluation of protocol adherence.

One-bead one-compound combinatorial library derived targeting ligands for detection and treatment of oral squamous cancer.

Oral squamous cancers (OSC) are hallmarked by poor prognosis, delayed clinical detection, and a lack of defined, characteristic biomarkers. By screening combinatorial one-bead one-compound (OBOC) peptide libraries against oral squamous cancer cell lines, two cyclic peptide ligands, LLY12 and LLY13 were previously identified. These ligands are capable of specific binding to the oral cancer cell lines (MOK-101, HSC-3, SCC-4 and SCC-10a) but not non-cancerous keratinocytes, leukocytes, fibroblast, and endothelial cells. These two peptides were synthesized and evaluated for their binding property, cytotoxicity and cell permeability. In vitro studies indicate that both LLY12 and LLY13 were able to bind to oral cancer cells with high specificity but did not show any cytotoxicity against human keratinocytes. Biotinylated LLY13, in complex with streptavidin-alexa488 was taken up by live oral cancer cells, thus rendering it as an excellent candidate vehicle for efficient delivery of drug loaded-nanoparticles. In vivo and ex vivo near infra-red fluorescence imaging studies confirmed the in vivo targeting efficiency and specificity of LLY13 in oral cancer orthotopic murine xenograft model. In vivo studies also showed that LLY13 was able to accumulate in the OSC tumors and demarcate the tumor margins in orthotopic xenograft model. Together, our data supports LLY13 as a promising theranostic agent against OSC.

Evaluating Response Time in Zanzibar's Malaria Elimination Case-Based Surveillance-Response System.

As countries transition toward malaria elimination, malaria programs rely on surveillance-response systems, which are often supported by web- and mobile phone-based reporting tools. Such surveillance-response systems are interventions for elimination, making it important to determine if they are operating optimally. A metric to measure this by is timeliness. This study used a mixed-methods approach to investigate the response time of Zanzibar's malaria elimination surveillance-response system, Malaria Case Notification (MCN). MCN conducts both passive and reactive case detection, supported by a mobile phone-based reporting tool called Coconut Surveillance. Using data obtained from RTI International and the Zanzibar Malaria Elimination Program (ZAMEP), analysis of summary statistics was conducted to investigate the association of response time with geography, and time series techniques were used to investigate trends in response time and its association with the number of reported cases. Results indicated that response time varied by the district in Zanzibar (0.6-6.05 days) and that it was not associated with calendar time or the number of reported cases. Survey responses and focus groups with a cadre of health workers, district malaria surveillance officers, shed light on operational challenges faced during case investigation, such as incomplete health records and transportation issues, which stem from deficiencies in aspects of ZAMEP's program management. These findings illustrate that timely response for malaria elimination depends on effective program management, despite the automation of web-based or mobile phone-based tools. For surveillance-response systems to work optimally, malaria programs should ensure that optimal management practices are in place.

Partnership Conference.

BACKGROUND: The Duke Global Health Institute (DGHI) was founded in 2006 with a goal to foster interdisciplinary global health education and research across Duke University and Duke Medical Center. Critical to achieving this goal is the need to develop and sustain strong international partnerships. OBJECTIVE: To host a conference with multiple international partners and strengthen existing relationships. METHODS: After a deliberate year-long planning process, DGHI convened a Partnership Conference with its international partners on the Duke University campus in conjunction with its 10th Anniversary Celebration. The Partnership Conference sought to promote an exchange of novel ideas in support of global health education and research, explore new collaborations in South-South relationships, and identify and facilitate pursuit of new educational and research opportunities. FINDINGS: A total of 25 partners from 10 countries and 46 DGHI faculty members participated in the 3-day event in October 2016. Activities included workshops on preselected research topics, educational symposia on novel teaching methods and harnessing technological advances, introduction of the Health Humanities Laboratory to prepare students and trainees for fieldwork, and discussions of research infrastructure and training needs. Surveys from visiting partners revealed a high degree of satisfaction. Proposed action items include methods to realize improved communications, enhancement of mutual education opportunities, support and mentoring to build local research capacity, and more exchange of faculty and students between partnering institutions. CONCLUSIONS: With careful planning from all parties, a multilateral partnership conference including both university and medical center faculty can be a productive forum for exchange on global health education and research. Sustaining such partnerships is vital to the success of global health scholarship.

A longitudinal cohort study of malaria exposure and changing serostatus in a malaria endemic area of rural Tanzania.

BACKGROUND: Measurements of anti-malarial antibodies are increasingly used as a proxy of transmission intensity. Most serological surveys are based on the use of cross-sectional data that, when age-stratified, approximates historical patterns of transmission within a population. Comparatively few studies leverage longitudinal data to explicitly relate individual infection events with subsequent antibody responses. METHODS: The occurrence of seroconversion and seroreversion events for two Plasmodium falciparum asexual stage antigens (MSP-1 and AMA-1) was examined using three annual measurements of 691 individuals from a cohort of individuals in a malaria-endemic area of rural east-central Tanzania. Mixed-effect logistic regression models were employed to determine factors associated with changes in serostatus over time. RESULTS: While the expected population-level relationship between seroprevalence and disease incidence was observed, on an individual level the relationship between individual infections and the antibody response was complex. MSP-1 antibody responses were more dynamic in response to the occurrence and resolution of infection events than AMA-1, while the latter was more correlated with consecutive infections. The MSP-1 antibody response to an observed infection seemed to decay faster over time than the corresponding AMA-1 response. Surprisingly, there was no evidence of an age effect on the occurrence of a conversion or reversion event. CONCLUSIONS: While the population-level results concur with previously published sero-epidemiological surveys, the individual-level results highlight the more complex relationship between detected infections and antibody dynamics than can be analysed using cross-sectional data. The longitudinal analysis of serological data may provide a powerful tool for teasing apart the complex relationship between infection events and the corresponding immune response, thereby improving the ability to rapidly assess the success or failure of malaria control programmes.

The Value of Information in Decision-Analytic Modeling for Malaria Vector Control in East Africa.

Decision analysis tools and mathematical modeling are increasingly emphasized in malaria control programs worldwide to improve resource allocation and address ongoing challenges with sustainability. However, such tools require substantial scientific evidence, which is costly to acquire. The value of information (VOI) has been proposed as a metric for gauging the value of reduced model uncertainty. We apply this concept to an evidenced-based Malaria Decision Analysis Support Tool (MDAST) designed for application in East Africa. In developing MDAST, substantial gaps in the scientific evidence base were identified regarding insecticide resistance in malaria vector control and the effectiveness of alternative mosquito control approaches, including larviciding. We identify four entomological parameters in the model (two for insecticide resistance and two for larviciding) that involve high levels of uncertainty and to which outputs in MDAST are sensitive. We estimate and compare a VOI for combinations of these parameters in evaluating three policy alternatives relative to a status quo policy. We find having perfect information on the uncertain parameters could improve program net benefits by up to 5-21%, with the highest VOI associated with jointly eliminating uncertainty about reproductive speed of malaria-transmitting mosquitoes and initial efficacy of larviciding at reducing the emergence of new adult mosquitoes. Future research on parameter uncertainty in decision analysis of malaria control policy should investigate the VOI with respect to other aspects of malaria transmission (such as antimalarial resistance), the costs of reducing uncertainty in these parameters, and the extent to which imperfect information about these parameters can improve payoffs.

Household perceptions and subjective valuations of indoor residual spraying programmes to control malaria in northern Uganda.

BACKGROUND: Insecticide-based tools remain critical for controlling vector-borne diseases in Uganda. Securing public support from targeted populations for such tools is an important component in sustaining their long-run effectiveness. Yet little quantitative evidence is available on the perceived benefits and costs of vector control programmes among targeted households. METHODS: A survey was administered to a clustered random sample of 612 households in Gulu and Oyam districts of northern Uganda during a period of very high malaria transmission and following a pilot indoor residual spray (IRS) programme. A discrete choice experiment was conducted within the survey, in which respondents indicated their preferences for different IRS programmes relative to money compensation in a series of experimentally controlled, hypothetical choice sets. The data were analysed using conditional logit regression models to estimate respondents' willingness to accept (WTA) some amount of money compensation in lieu of foregone malaria risk reductions. Latent class models were used to analyse whether respondent characteristics predicted WTA. RESULTS: Average WTA is estimated at $8.94 annually for a 10 % reduction in malaria risk, and additional co-benefits of IRS were estimated to be worth on average $54-$56 (depending on insecticide type) per round of IRS. Significant heterogeneity is observed: Four in five household heads in northern Uganda have high valuations for IRS programmes, while the remaining 20 % experience costly side effects of IRS (valued at between $2 and $3 per round). Statistically significant predictors of belonging to the high-value group include respondent gender, mean age of household members, participation in previous IRS, basic knowledge of mosquito reproduction, and the number of mosquito nets owned. Proxies for household income and wealth are not found to be statistically significant predictors of WTA. CONCLUSIONS: This study suggests that the majority of people in areas of high malaria transmission like northern Uganda place a high value on vector control programmes using IRS. However, there is significant heterogeneity in terms of the perceived side effects (positive and negative). This has implications for sustaining public support for these programmes in the long-term.

Cost of microbial larviciding for malaria control in rural Tanzania.

OBJECTIVE: Microbial larviciding may be a potential supplement to conventional malaria vector control measures, but scant information on its relative implementation costs and effectiveness, especially in rural areas, is an impediment to expanding its uptake. We perform a costing analysis of a seasonal microbial larviciding programme in rural Tanzania. METHODS: We evaluated the financial and economic costs from the perspective of the public provider of a 3-month, community-based larviciding intervention implemented in twelve villages in the Mvomero District of Tanzania in 2012-2013. Cost data were collected from financial reports and invoices and through discussion with programme administrators. Sensitivity analysis explored the robustness of our results to varying key parameters. RESULTS: Over the 2-year study period, approximately 6873 breeding sites were treated with larvicide. The average annual economic costs of the larviciding intervention in rural Tanzania are estimated at 2014 US$ 1.44 per person protected per year (pppy), US$ 6.18 per household and US$ 4481.88 per village, with the larvicide and staffing accounting for 14% and 58% of total costs, respectively. CONCLUSIONS: We found the costs pppy of implementing a seasonal larviciding programme in rural Tanzania to be comparable to the costs of other larviciding programmes in urban Tanzania and rural Kenya. Further research should evaluate the cost-effectiveness of larviciding relative to, and in combination with, other vector control strategies in rural settings.

Identifying barriers in the malaria control policymaking process in East Africa: insights from stakeholders and a structured literature review.

BACKGROUND: The complexity of malaria and public health policy responses presents social, financial, cultural, and institutional barriers to policymaking at multiple stages in the policy process. These barriers reduce the effectiveness of health policy in achieving national goals. METHODS: We conducted a structured literature review to characterize malaria policy barriers, and we engaged stakeholders through surveys and workshops in Kenya, Tanzania, and Uganda. We compared common barriers presented in the scientific literature to barriers reported by malaria policy stakeholders. RESULTS: The barriers identified in the structured literature review differ from those described in policymaker surveys. The malaria policy literature emphasizes barriers in the implementation stage of policymaking such as those posed by health systems and specific intervention tools. Stakeholder responses placed greater emphasis on the political nature of policymaking, the disconnect between research and policymaking, and the need for better intersectoral collaboration. CONCLUSIONS: Identifying barriers to effective malaria control activities provides opportunities to improve health and other outcomes. Such barriers can occur at multiple stages and scales. Employing a stakeholder - designed decision tool framework has the potential to improve existing policies and ultimately the functioning of malaria related institutions. Furthermore, improved coordination between malaria research and policymaking would improve the quality and efficiency of interventions leading to better population health.

Sustaining the gains made in malaria control and elimination.

Significant progress has been made in the last 25 years to reduce the malaria burden, but considerable challenges remain. These gains have resulted from large investments in a range of control measures targeting malaria. Fana and co-authors find a strong relationship between education level and net usage with malaria parasitemia in pregnant women, suggesting the need for targeted control strategies. Mayala and co-workers find important links between agriculture and malaria with implications for inter-sectoral collaboration for malaria control.

Feasibility and roadmap analysis for malaria elimination in China.

To understand the current status of the malaria control programme at the county level in accordance with the criteria of the World Health Organisation, the gaps and feasibility of malaria elimination at the county and national levels were analysed based on three kinds of indicators: transmission capacity, capacity of the professional team, and the intensity of intervention. Finally, a roadmap for national malaria elimination in the People's Republic of China is proposed based on the results of a feasibility assessment at the national level.

Lessons from malaria control to elimination: case study in Hainan and Yunnan provinces.

Reduction patterns of Plasmodium falciparum and P. vivax malaria transmission and the role of an integrated strategy of case management and vector control are compared between different ecological zones. The epidemiology of malaria in Hainan and Yunnan provinces was disparate, even though distinct malaria control strategies have been adapted to different situations based on risk group, vector behaviours, local health infrastructure, and environmental conditions. The island Hainan appears to be victorious in eliminating malaria. However, there is still a long way to go to prevent the reintroduction of malaria in Hainan province and eliminating malaria in the border areas of Yunnan province. This review of the experiences and challenges from malaria control to elimination in Hainan and Yunnan provinces of southern China will provide a basis for the future elimination of malaria in the whole country.

Factors influencing malaria control policy-making in Kenya, Uganda and Tanzania.

BACKGROUND: Policy decisions for malaria control are often difficult to make as decision-makers have to carefully consider an array of options and respond to the needs of a large number of stakeholders. This study assessed the factors and specific objectives that influence malaria control policy decisions, as a crucial first step towards developing an inclusive malaria decision analysis support tool (MDAST). METHODS: Country-specific stakeholder engagement activities using structured questionnaires were carried out in Kenya, Uganda and Tanzania. The survey respondents were drawn from a non-random purposeful sample of stakeholders, targeting individuals in ministries and non-governmental organizations whose policy decisions and actions are likely to have an impact on the status of malaria. Summary statistics across the three countries are presented in aggregate. RESULTS: Important findings aggregated across countries included a belief that donor preferences and agendas were exerting too much influence on malaria policies in the countries. Respondents on average also thought that some relevant objectives such as engaging members of parliament by the agency responsible for malaria control in a particular country were not being given enough consideration in malaria decision-making. Factors found to influence decisions regarding specific malaria control strategies included donor agendas, costs, effectiveness of interventions, health and environmental impacts, compliance and/acceptance, financial sustainability, and vector resistance to insecticides. CONCLUSION: Malaria control decision-makers in Kenya, Uganda and Tanzania take into account health and environmental impacts as well as cost implications of different intervention strategies. Further engagement of government legislators and other policy makers is needed in order to increase funding from domestic sources, reduce donor dependence, sustain interventions and consolidate current gains in malaria.

Community knowledge and acceptance of larviciding for malaria control in a rural district of east-central Tanzania.

The use of microbial larvicides, a form of larval source management, is a less commonly used malaria control intervention that nonetheless has significant potential as a component of an integrated vector management strategy. We evaluated community acceptability of larviciding in a rural district in east-central Tanzania using data from 962 household surveys, 12 focus group discussions, and 24 in-depth interviews. Most survey respondents trusted in the safety (73.1%) and efficacy of larviciding, both with regards to mosquito control (92.3%) and to reduce malaria infection risk (91.9%). Probing these perceptions using a Likert scale provides a more detailed picture. Focus group participants and key informants were also receptive to larviciding, but stressed the importance of sensitization before its implementation. Overall, 73.4% of survey respondents expressed a willingness to make a nominal household contribution to a larviciding program, a proportion which decreased as the proposed contribution increased. The lower-bound mean willingness to pay is estimated at 2,934 Tanzanian Shillings (approximately US$1.76) per three month period. We present a multivariate probit regression analysis examining factors associated with willingness to pay. Overall, our findings point to a receptive environment in a rural setting in Tanzania for the use of microbial larvicides in malaria control.

A randomized longitudinal factorial design to assess malaria vector control and disease management interventions in rural Tanzania.

The optimization of malaria control strategies is complicated by constraints posed by local health systems, infrastructure, limited resources, and the complex interactions between infection, disease, and treatment. The purpose of this paper is to describe the protocol of a randomized factorial study designed to address this research gap. This project will evaluate two malaria control interventions in Mvomero District, Tanzania: (1) a disease management strategy involving early detection and treatment by community health workers using rapid diagnostic technology; and (2) vector control through community-supported larviciding. Six study villages were assigned to each of four groups (control, early detection and treatment, larviciding, and early detection and treatment plus larviciding). The primary endpoint of interest was change in malaria infection prevalence across the intervention groups measured during annual longitudinal cross-sectional surveys. Recurring entomological surveying, household surveying, and focus group discussions will provide additional valuable insights. At baseline, 962 households across all 24 villages participated in a household survey; 2,884 members from 720 of these households participated in subsequent malariometric surveying. The study design will allow us to estimate the effect sizes of different intervention mixtures. Careful documentation of our study protocol may also serve other researchers designing field-based intervention trials.