EVALUATING A REACTIVE TEST-AND-TREAT PROGRAM FOR SUB-PATENT MALARIA IN MACHA, ZAMBIA: OPTIMAL STRATEGIES TO ACHIEVE ELIMINATION

Background: In Choma District, Southern Province, Zambia, malaria prevalence by rapid diagnostic test (RDT) declined from 8% in 2008 to 1% in 2013. As part of an effort to achieve elimination, the Zambian government implemented a reactive test-and-treat (RTAT) program in parts of Southern Province in 2013. Individuals with confirmed malaria by health workers are followed-up within two weeks of diagnosis. All individuals living in households within 140 meters of the index case are tested with an RDT and treated if positive. This study aimed to optimize the RTAT strategy by characterizing infected individuals missed by both the RDT and the current screening radius. Methods: Health workers notified the study team of individuals with RDT confirmed malaria. For each study participant, a questionnaire was administered and a blood sample collected. To evaluate the optimal RTAT radius and assess the frequency of sub-patent, RDT negative infections, the radius was expanded to 250 meters and testing of dried blood spot samples by real-time polymerase chain reaction (PCR) was introduced. Spatial-temporal cluster detection was conducted to identify clusters of index households. Results: From January 2015 to January 2016, 101 index cases were followed-up through the RTAT program. 2504 individuals residing in 394 households were screened. Excluding index cases, parasite prevalence was 2.5% by PCR (53 of 2225) and 1.2% by RDT (26 of 2108). 66% of PCR positive individuals tested negative by RDT. 24 households had a PCR+/RDT- individual. Nearly half of those infected resided within the index case household. No clustering of index house was identified. Conclusion: The low number of secondary cases indicates a low efficiency of RTAT beyond the index case household in this setting, and the sensitivity of the RDT was too low to be an effective screening tool. Focal drug administration in which all individuals within index case households are treated may be a more efficient approach to achieving malaria elimination in southern Zambia

THE CHANGING SPATIAL EPIDEMIOLOGY OF MALARIA IN THE DEMOCRATIC REPUBLIC OF THE CONGO

Malaria remains a significant public health problem worldwide, and especially in the Democratic Republic of the Congo (DRC), where approximately 12% of global cases occur. Despite this burden, very few national malaria studies have been conducted in the DRC, particularly amongst adults. Because of this, critical questions, such who is at highest risk and where transmission is highest, remain under-studied. This information is needed to tailor interventions to individuals and areas in which they will be most effective. We aimed to fill this gap in the literature using data from the population based, nationally-representative Demographic and Health Surveys (DHS) conducted in the DRC. Using DHS data, we evaluated the status of malaria prevalence amongst adults in the DRC, and determine changes in prevalence over time. We found that the national prevalence is high, approximately 30%, and that the prevalence of patent infections increased from 2.4% in 2007 to 7.5% in 2013. We identified several risk factors for infection, such as traditional housing and decreased within-household net coverage. However, we also found that while uptake of malaria interventions has increased since 2007, use of long-lasting insecticide treated nets (LLIN) and intermittent preventative therapy during pregnancy both remain low. Increasing LLIN use was associated with only a small reduction in prevalence of patent infection, pointing to the need to re-evaluate current malaria control strategies. Overall, this dissertation highlights the high prevalence of infections amongst adults and the need for massively scaled up malaria control efforts. The findings identify individuals and areas that most need attention. These findings will help the DRC Ministry of Health plan future malaria control programs and help ensure that such programs are maximally effective. This dissertation also underscore the importance of studying malaria amongst individuals of all ages.Doctor of Philosoph

Transmission of Mycobacterium tuberculosis to Healthcare Personnel Resulting From Contaminated Bone Graft Material, United States, June 2021–August 2022

A nationwide tuberculosis outbreak linked to a viable bone allograft product contaminated with Mycobacterium tuberculosis was identified in June 2021. Our subsequent investigation identified 73 healthcare personnel with new latent tuberculosis infection following exposure to the contaminated product, product recipients, surgical instruments, or medical waste

Low Complexity of Infection Is Associated With Molecular Persistence of Plasmodium falciparum in Kenya and Tanzania

Background Plasmodium falciparum resistance to artemisinin-based combination therapies (ACTs) is a threat to malaria elimination. ACT-resistance in Asia raises concerns for emergence of resistance in Africa. While most data show high efficacy of ACT regimens in Africa, there have been reports describing declining efficacy, as measured by both clinical failure and prolonged parasite clearance times. Methods Three hundred children aged 2–10 years with uncomplicated P. falciparum infection were enrolled in Kenya and Tanzania after receiving treatment with artemether-lumefantrine. Blood samples were taken at 0, 24, 48, and 72 h, and weekly thereafter until 28 days post-treatment. Parasite and host genetics were assessed, as well as clinical, behavioral, and environmental characteristics, and host anti-malarial serologic response. Results While there was a broad range of clearance rates at both sites, 85% and 96% of Kenyan and Tanzanian samples, respectively, were qPCR-positive but microscopy-negative at 72 h post-treatment. A greater complexity of infection (COI) was negatively associated with qPCR-detectable parasitemia at 72 h (OR: 0.70, 95% CI: 0.53–0.94), and a greater baseline parasitemia was marginally associated with qPCR-detectable parasitemia (1,000 parasites/uL change, OR: 1.02, 95% CI: 1.01–1.03). Demographic, serological, and host genotyping characteristics showed no association with qPCR-detectable parasitemia at 72 h. Parasite haplotype-specific clearance slopes were grouped around the mean with no association detected between specific haplotypes and slower clearance rates. Conclusions Identifying risk factors for slow clearing P. falciparum infections, such as COI, are essential for ongoing surveillance of ACT treatment failure in Kenya, Tanzania, and more broadly in sub-Saharan Africa

Effects of handling and vehicle injections on adrenocorticotropic and corticosterone concentrations in Sprague-Dawley compared with Lewis rats.

The hypothalamic-pituitary-adrenal (HPA) axis is a key factor in the trajectory of the addiction-like cycle (a pattern of behavior characterized by escalating drug use, withdrawal, and relapse) in preclinical and clinical studies. Concentrations of HPA hormones change in laboratory animals in response to standard experimental procedures, including handling and vehicle injections. We compared HPA activity in adult male Lewis (inbred) and Sprague-Dawley (outbred) rats, 2 common strains in rodent models of addiction, after different schedules of handling and saline injections, to explore the extent to which HPA responses differ by strain and whether interindividual differences underlie addiction vulnerability. The 4 treatment conditions were no, short, or long handling and saline injections. In handled groups, rats were handled for 1 to 2 min for 3 times daily and were euthanized after 7 d (short handling) or 14 d (long handling). The injection schedule in the saline injection group mimicked that in a model of binge-like cocaine exposure. Across all treatment groups, concentrations of adrenocorticotropic hormone were higher in Sprague-Dawley than in Lewis rats. In Sprague-Dawley rats, corticosterone concentrations decreased after continued handling but remained constant in Lewis rats. Interindividual variability in hormone levels was greater in Sprague-Dawley than Lewis rats, although corticosterone variability decreased after continued handling. Prolactin did not differ between groups of either Sprague-Dawley and Lewis rats before or after handling. This study underscores the importance of prolonged handling before experimenter-provided drug-administration paradigms and of strain-associated differences that may affect study outcomes

Rapid assessment of institutional research ethics capacity: A case study from Zambia

© 2017, Organizacion Panamericana de la Salud. All rights reserved. Recently, there has been a remarkable increase in biomedical research being conducted in low and middle-income countries. This increase has brought attention to the need for high quality research ethics systems within these countries and a greater focus on research ethics training. Though most programs tend to concentrate on training individuals, less attention has focused on institutions as the target of such training. In this paper we demonstrate a rapid approach to evaluating institutional research capacity. The method adapts the Octagon Model, which evaluates institutional research ethics using eight domains. The framework was applied to the University of Zambia in order to conduct a baseline assessment of university research ethics capacity. Internal and external assessments were conducted. The domains of working environment and proper skills scored highest, while relevance, target groups and identity scored lower. Consistent with previous work, a systems approach to evaluating institutional research development capacity can provide a rapid assessment of an institutional bioethics program. This case study reveals the strengths and weaknesses of the university’s research ethics program and provides a framework for future capacity growth

Improving institutional research ethics capacity assessments: lessons from sub-Saharan Africa

The amount of biomedical research being conducted around the world has greatly expanded over the past 15 years, with particularly large growth occurring in low- and middle-income countries (LMICs). This increased focus on understanding and responding to disease burdens around the world has brought forth a desire to help LMIC institutions enhance their own capacity to conduct scientifically and ethically sound research. In support of these goals the Johns Hopkins-Fogarty African Bioethics Training Program (FABTP) has, for the past six years, partnered with three research institutions in Africa (University of Botswana, Makerere University in Uganda, and the University of Zambia) to support research ethics capacity. Each partnership began with a baseline evaluation of institutional research ethics environments in order to properly tailor capacity strengthening activities and help direct limited institutional resources. Through the course of these partnerships we have learned several lessons regarding the evaluation process and the framework used to complete the assessments (the Octagon Model). We believe that these lessons are generalizable and will be useful for groups conducting such assessments in the future

Ethics considerations in global mobile phone-based surveys of noncommunicable diseases:A conceptual exploration

© 2017 Adrian Aguilera, Emma Bruehlman-Senecal, Orianna Demasi, Patricia Avila. Mobile phone coverage has grown, particularly within low-And middle-income countries (LMICs), presenting an opportunity to augment routine health surveillance programs. Several LMICs and global health partners are seeking opportunities to launch basic mobile phone-based surveys of noncommunicable diseases (NCDs). The increasing use of such technology in LMICs brings forth a cluster of ethical challenges; however, much of the existing literature regarding the ethics of mobile or digital health focuses on the use of technologies in high-income countries and does not consider directly the specific ethical issues associated with the conduct of mobile phone surveys (MPS) for NCD risk factor surveillance in LMICs. In this paper, we explore conceptually several of the central ethics issues in this domain, which mainly track the three phases of the MPS process: predata collection, during data collection, and postdata collection. These include identifying the nature of the activity; stakeholder engagement; appropriate design; anticipating and managing potential harms and benefits; consent; reaching intended respondents; data ownership, access and use; and ensuring LMIC sustainability. We call for future work to develop an ethics framework and guidance for the use of mobile phones for disease surveillance globally

Evaluation of health system readiness and coverage of intermittent preventive treatment of malaria in infants (IPTi) in Kambia district to inform national scale-up in Sierra Leone

Background Intermittent preventive treatment of malaria in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is a proven strategy to protect infants against malaria. Sierra Leone is the first country to implement IPTi nationwide. IPTi implementation was evaluated in Kambia, one of two initial pilot districts, to assess quality and coverage of IPTi services. Methods This mixed-methods evaluation had two phases, conducted 3 (phase 1) and 15–17 months (phase 2) after IPTi implementation. Methods included: assessments of 18 health facilities (HF), including register data abstraction (phases 1 and 2); a knowledge, attitudes and practices survey with 20 health workers (HWs) in phase 1; second-generation sequencing of SP resistance markers (pre-IPTi and phase 2); and a cluster-sample household survey among caregivers of children aged 3–15 months (phase 2). IPTi and vaccination coverage from the household survey were calculated from child health cards and maternal recall and weighted for the complex sampling design. Interrupted time series analysis using a Poisson regression model was used to assess changes in malaria cases at HF before and after IPTi implementation. Results Most HWs (19/20) interviewed had been trained on IPTi; 16/19 reported feeling well prepared to administer it. Nearly all HFs (17/18 in phase 1; 18/18 in phase 2) had SP for IPTi in stock. The proportion of parasite alleles with dhps K540E mutations increased but remained below the 50% WHO-recommended threshold for IPTi (4.1% pre-IPTi [95%CI 2–7%]; 11% post-IPTi [95%CI 8–15%], p < 0.01). From the household survey, 299/459 (67.4%) children ≥ 10 weeks old received the first dose of IPTi (versus 80.4% for second pentavalent vaccine, given simultaneously); 274/444 (62.5%) children ≥ 14 weeks old received the second IPTi dose (versus 65.4% for third pentavalent vaccine); and 83/217 (36.4%) children ≥ 9 months old received the third IPTi dose (versus 52.2% for first measles vaccine dose). HF register data indicated no change in confirmed malaria cases among infants after IPTi implementation. Conclusions Kambia district was able to scale up IPTi swiftly and provide necessary health systems support. The gaps between IPTi and childhood vaccine coverage need to be further investigated and addressed to optimize the success of the national IPTi programme