How prepared is the world? Identifying weaknesses in existing assessment frameworks for global health security through a One Health approach.

The COVID-19 pandemic has exposed faults in the way we assess preparedness and response capacities for public health emergencies. Existing frameworks are limited in scope, and do not sufficiently consider complex social, economic, political, regulatory, and ecological factors. One Health, through its focus on the links among humans, animals, and ecosystems, is a valuable approach through which existing assessment frameworks can be analysed and new ways forward proposed. Although in the past few years advances have been made in assessment tools such as the International Health Regulations Joint External Evaluation, a rapid and radical increase in ambition is required. To sufficiently account for the range of complex systems in which health emergencies occur, assessments should consider how problems are defined across stakeholders and the wider sociopolitical environments in which structures and institutions operate. Current frameworks do little to consider anthropogenic factors in disease emergence or address the full array of health security hazards across the social-ecological system. A complex and interdependent set of challenges threaten human, animal, and ecosystem health, and we cannot afford to overlook important contextual factors, or the determinants of these shared threats. Health security assessment frameworks should therefore ensure that the process undertaken to prioritise and build capacity adheres to core One Health principles and that interventions and outcomes are assessed in terms of added value, trade-offs, and cobenefits across human, animal, and environmental health systems.

Could vaccinating adults against malaria materially reduce adult mortality in high-transmission areas?

After a period of unprecedented progress against malaria in the 2000s, halving the global disease burden by 2015, gains overall in sub-Saharan Africa have slowed and even reversed in some places, beginning well before the COVID-19 pandemic. The highly effective drugs, treated nets, and diagnostics that fueled the initial progress all face some threats to their effectiveness, and global funding to maintain and increase their use over the long term is not guaranteed. Malaria vaccines are among the most promising new interventions that could accelerate the elimination of malaria. Vaccines are still in early stages of rollout in children, the age group (along with pregnant women) that has been the focus of malaria strategies for a century. At the same time, over the past decade, a case has been made, based largely on evidence from verbal autopsies in at least a few high-transmission areas, that the malaria death rate among adults has been greatly underestimated. Could vaccinating adults help to bring down the adult malaria mortality rate, contribute to reduced transmission, or both? A randomized trial of a malaria vaccine is proposed in Sierra Leone, a highly endemic setting, to shed light on this proposition.

An ethics of anthropology-informed community engagement with COVID-19 clinical trials in Africa.

The COVID-19 pandemic has reinforced the critical role of ethics and community engagement in designing and conducting clinical research during infectious disease outbreaks where no vaccine or treatment already exists. In reviewing current practices across Africa, we distinguish between three distinct roles for community engagement in clinical research that are often conflated: 1) the importance of community engagement for identifying and honouring cultural sensitivities; 2) the importance of recognising the socio-political context in which the research is proposed; and 3) the importance of understanding what is in the interest of communities recruited to research according to their own views and values. By making these distinctions, we show that current practice of clinical research could draw on anthropology in ways which are sometimes unnecessary to solicit local cultural values, overlook the importance of socio-political contexts and wider societal structures within which it works, potentially serving to reinforce unjust political or social regimes, and threaten to cast doubt on the trustworthiness of the research. We argue that more discerning anthropological engagement as well as wider collaboration with other social scientists and those working in the humanities is urgently needed to improve the ethics of current biomedical and pharmaceutical research practice in Africa.

Are malaria transmission-blocking vaccines acceptable to high burden communities? Results from a mixed methods study in Bo, Sierra Leone.

BACKGROUND: Malaria transmission-blocking vaccines (TBVs) could help break the cycle of malaria transmission by conferring community rather than individual protection. When introducing new intervention strategies, uptake is dependent on acceptability, not just efficacy. In this exploratory study on acceptability of TBVs in Sierra Leone, it was hypothesized that TBVs would be largely acceptable to adults and health workers in areas with relatively few ongoing malaria interventions, and that (i) knowledge of malaria and vaccines, (ii) health behaviours associated with malaria and vaccines, and (iii) attitudes towards different vaccines types could lead to greater TBV acceptability. METHODS: This study used a mixed methods approach in Bo, Sierra Leone, to understand community knowledge, attitudes, and practices related to malaria and vaccination in general. This included: (i) a population-based cross-sectional survey (n=615 adults), (ii) 6 focus group discussions with parents, and (iii) 20 key informant interviews. The concept of a TBV was explained to participants before they were asked about their willingness to accept this vaccine modality as part of an integrated malaria elimination programme. RESULTS: This study found that most adults would be willing to receive a TBV vaccine. Respondents noted mostly positive past experiences with adult and childhood vaccinations for other infectious diseases and high levels of engagement in other malaria prevention behaviors such as bed nets. Perceived barriers to TBV acceptance were largely focused on general community-level distribution of a vaccine, including personal fears of vaccination and possible costs. After an explanation of the TBV mechanism, nearly all focus group and interview participants believed that community members would accept the vaccine as part of an integrated malaria control approach. Both parents and health workers offered insight on how to successfully roll-out a future TBV vaccination programme. CONCLUSIONS: The willingness of community members in Bo, Sierra Leone to accept a TBV as part of an integrated anti-malarial strategy suggests that the atypical mechanism of TBV action might not be an obstacle to future clinical trials. This study's findings suggests that perceived general barriers to vaccination implementation, such as perceived personal fears and vaccine cost, must be addressed in future clinical and implementation research studies.

Comparison of capillary and venous blood for malaria detection using two PCR-based assays in febrile patients in Sierra Leone.

BACKGROUND: Rapid and sensitive diagnostics are critical tools for clinical case management and public health control efforts. Both capillary and venous blood are currently used for malaria detection and while diagnostic technologies may not be equally sensitive with both materials, the published data on this subject are scarce and not conclusive. METHODS: Paired clinical samples of venous and capillary blood from 141 febrile individuals in Bo, Sierra Leone, were obtained between January and May 2019 and tested for the presence of Plasmodium parasites using two multiplexed PCR assays: the FilmArray-based Global Fever Panel (GFP) and the TaqMan-based Malaria Multiplex Sample Ready (MMSR) assay. RESULTS: No significant differences in Plasmodium parasite detection between capillary and venous blood for both assays were observed. The GFP assay was more sensitive than MMSR for all markers that could be compared (Plasmodium spp. and Plasmodium falciparum) in both venous and capillary blood. CONCLUSIONS: No difference was found in malaria detection between venous and capillary blood using two different PCR-based detection assays. This data gives support for use of capillary blood, a material which can be obtained easier by less invasive methods, for PCR-based malaria diagnostics, independent of the platform.

The niche of One Health approaches in Lassa fever surveillance and control.

Lassa fever (LF), a zoonotic illness, represents a public health burden in West African countries where the Lassa virus (LASV) circulates among rodents. Human exposure hinges significantly on LASV ecology, which is in turn shaped by various parameters such as weather seasonality and even virus and rodent-host genetics. Furthermore, human behaviour, despite playing a key role in the zoonotic nature of the disease, critically affects either the spread or control of human-to-human transmission. Previous estimations on LF burden date from the 80s and it is unclear how the population expansion and the improvement on diagnostics and surveillance methods have affected such predictions. Although recent data have contributed to the awareness of epidemics, the real impact of LF in West African communities will only be possible with the intensification of interdisciplinary efforts in research and public health approaches. This review discusses the causes and consequences of LF from a One Health perspective, and how the application of this concept can improve the surveillance and control of this disease in West Africa.

A mixed-methods investigation to understand and improve the scaled-up infection prevention and control in primary care health facilities during the Ebola virus disease epidemic in Sierra Leone.

BACKGROUND: The 2014-2015 Ebola epidemic in West Africa became a humanitarian crisis that exposed significant gaps in infection prevention and control (IPC) capacity in primary care facilities in Sierra Leone. Operational partners recognized the national gap and rapidly scaled-up an IPC training and infrastructure package. This prompted us to carry out a mixed-methods research study which aimed to evaluate adherence to IPC practices and understand how to improve IPC at the primary care level, where most cases of Ebola were initially presenting. The study was carried out during the national peak of the epidemic. DISCUSSION: We successfully carried out a rapid response research study that produced several expected and unexpected findings that were used to guide IPC measures during the epidemic. Although many research challenges were similar to those found when conducting research in low-resource settings, the presence of Ebola added risks to safety and security of data collectors, as well as a need to balance research activities with the imperative of response to a humanitarian crisis. A participatory approach that attempted to unify levels of the response from community upwards helped overcome the risk of lack of trust in an environment where Ebola had damaged relations between communities and the health system. CONCLUSION: In the context of a national epidemic, research needs to be focused, appropriately resourced, and responsive to needs. The partnership between local academics and a humanitarian organization helped facilitate access to study sites and approvals that allowed the research to be carried out quickly and safely, and for findings to be shared in response forums with the best chance of being taken up in real-time.

Prevalence and socio-demographic associations of diet and physical activity risk-factors for cardiovascular disease in Bo, Sierra Leone.

BACKGROUND: Little is known about modifiable dietary and physical activity risk factors for cardiovascular diseases (CVDs) in Sierra Leone. This information is critical to the development of health improvement interventions to reduce the prevalence of these diseases. This cross-sectional study investigated the prevalence and socio-demographic correlates of dietary and physical activity risk behaviours amongst adults in Bo District, Sierra Leone. METHODS: Adults aged 40+ were recruited from 10 urban and 30 rural sub-districts in Bo. We examined risk factors including: ≤150 min of moderate or vigorous-intensity physical activity (MVPA) weekly, physical inactivity for ≥3 h daily, ≤5 daily portions of fruit and vegetables, and salt consumption (during cooking, at the table, and in salty snacks). We used logistic regression to investigate the relationship between these outcomes and participants' socio-demographic characteristics. RESULTS: 1978 eligible participants (39.1% urban, 55.6% female) were included in the study. The prevalence of behavioural risk factors was 83.6% for ≤5 daily portions of fruit and vegetables; 41.4 and 91.6% for adding salt at the table or during cooking, respectively and 31.1% for eating salty snacks; 26.1% for MVPA ≤150 min weekly, and 45.6% for being physically inactive ≥3 h daily. Most MVPA was accrued at work (nearly 24 h weekly). Multivariable analysis showed that urban individuals were more likely than rural individuals to consume ≤5 daily portions of fruit and vegetables (Odds Ratio (OR) 1.09, 95% Confidence Interval (1.04-1.15)), add salt at the Table (OR 1.88 (1.82-1.94)), eat salty snacks (OR 2.00 (1.94-2.07)), and do MVPA ≤150 min weekly (OR 1.16 (1.12-1.21)). Male individuals were more likely to add salt at the Table (OR 1.23 (1.20-1.27)) or consume salty snacks (OR 1.35 (1.31-1.40)) than female individuals but were less likely to report the other behavioural risk-factors examined. Generally, people in lower wealth quintiles had lower odds of each risk factor than those in the higher wealth quintiles. CONCLUSION: Dietary risk factors for CVD are highly prevalent, particularly among urban residents, of Bo District, Sierra Leone. Our findings highlight that forthcoming policies in Sierra Leone need to consider modifiable risk factors for CVD in the context of urbanisation.

Use of real-time multiplex PCR, malaria rapid diagnostic test and microscopy to investigate the prevalence of Plasmodium species among febrile hospital patients in Sierra Leone.

BACKGROUND: Malaria continues to affect over 200 million individuals every year, especially children in Africa. Rapid and sensitive detection and identification of Plasmodium parasites is crucial for treating patients and monitoring of control efforts. Compared to traditional diagnostic methods such as microscopy and rapid diagnostic tests (RDTs), DNA based methods, such as polymerase chain reaction (PCR) offer significantly higher sensitivity, definitive discrimination of Plasmodium species, and detection of mixed infections. While PCR is not currently optimized for routine diagnostics, its role in epidemiological studies is increasing as the world moves closer toward regional and eventually global malaria elimination. This study demonstrates the field use of a novel, ambient temperature-stabilized, multiplexed PCR assay in a small hospital setting in Sierra Leone. METHODS: Blood samples from 534 febrile individuals reporting to a hospital in Bo, Sierra Leone, were tested using three methods: a commercial RDT, microscopy, and a Multiplex Malaria Sample Ready (MMSR) PCR designed to detect a universal malaria marker and species-specific markers for Plasmodium falciparum and Plasmodium vivax. A separate PCR assay was used to identify species of Plasmodium in samples in which MMSR detected malaria, but was unable to identify the species. RESULTS: MMSR detected the presence of any malaria marker in 50.2% of all tested samples with P. falciparum identified in 48.7% of the samples. Plasmodium vivax was not detected. Testing of MMSR P. falciparum-negative/universal malaria-positive specimens with a panel of species-specific PCRs revealed the presence of Plasmodium malariae (n = 2) and Plasmodium ovale (n = 2). The commercial RDT detected P. falciparum in 24.6% of all samples while microscopy was able to detect malaria in 12.8% of tested specimens. CONCLUSIONS: Wider application of PCR for detection of malaria parasites may help to fill gaps existing as a result of use of microscopy and RDTs. Due to its high sensitivity and specificity, species coverage, room temperature stability and relative low complexity, the MMSR assay may be useful for detection of malaria and epidemiological studies especially in low-resource settings.

Estimating the size of urban populations using Landsat images: a case study of Bo, Sierra Leone, West Africa.

BACKGROUND: This is the third paper in a 3-paper series evaluating alternative models for rapidly estimating neighborhood populations using limited survey data, augmented with aerial imagery. METHODS: Bayesian methods were used to sample the large solution space of candidate regression models for estimating population density. RESULTS: We accurately estimated the population densities and counts of 20 neighborhoods in the city of Bo, Sierra Leone, using statistical measures derived from Landsat multi-band satellite imagery. The best regression model proposed estimated the latter with an absolute median proportional error of 8.0%, while the total population of the 20 neighborhoods was estimated with an error of less than 1.0%. We also compare our results with those obtained using an empirical Bayes approach. CONCLUSIONS: Our approach provides a rapid and effective method for constructing predictive models for population densities and counts utilizing remote sensing imagery. Our results, including cross-validation analysis, suggest that masking non-urban areas in the Landsat section images prior to computing the candidate covariate regressors should further improve model generality.

"We and the nurses are now working with one voice": How community leaders and health committee members describe their role in Sierra Leone's Ebola response.

BACKGROUND: Across low-income settings, community volunteers and health committee members support the formal health system - both routinely and amid emergencies - by engaging in health services such as referrals and health education. During the 2014-2015 Ebola epidemic, emerging reports suggest that community engagement was instrumental in interrupting transmission. Nevertheless, literature regarding community volunteers' roles during emergencies generally, and Ebola specifically, is scarce. This research outlines what this cadre of the workforce did, how they coped, and the facilitators and barriers they faced to providing care in Sierra Leone. METHODS: Thirteen focus group discussions (FGD) were conducted with community members (including members of Health Management Committees (HMC)) near the height of the Ebola epidemic in two districts of Sierra Leone: Bo and Kenema. Conducted in either Krio or Mende, each FGD lasted an average of two hours and was led by a trained moderator who was accompanied by a note taker. All FGDs were audio recorded, transcribed, and translated into English by the data collection team. Analysis followed a modified framework approach, which entailed coding (both inductive and deductive), arrangement of codes into themes, and drafting, distribution and discussion of analytic summaries across the study team. RESULTS: Community volunteers and HMC members described engaging in labor-related tasks (e.g. building isolation structures, digging graves) and administrative/community-outreach tasks (e.g. screening, contact tracing, and encouraging care seeking within facilities). Through their dual orientation as community members and as individuals linked to the health system, respondents described building community trust and support for Ebola prevention and treatment, while also enabling formal health workers to better understand and address people's fears and needs. Community volunteers' main concerns included inadequate communication with - and a sense of being forgotten by - the health system, negative perceptions of their role within their communities, and concerns regarding the amount and nature of their compensation. DISCUSSION & CONCLUSION: Respondents described commitment to supporting their health system and their communities during the Ebola crisis. The health system could more effectively harness the potential of local responders by recognizing community strengths and weaknesses, as well as community volunteers' motivations and limitations. Clarifying the roles, responsibilities, and remuneration of health volunteers to the recipients themselves, facility-based staff, and the wider community will enable organizations that partner with health committees to bolster trust, manage expectations, and reinforce collaboration.

Prevalence of Quinolone Resistance in Enterobacteriaceae from Sierra Leone and the Detection of qnrB Pseudogenes and Modified LexA Binding Sites.

A collection of 74 Enterobacteriaceae isolates found in Bo, Sierra Leone, were tested for quinolone antibiotic susceptibility and resistance mechanisms. The majority of isolates (62%) were resistant to quinolones, and 61% harbored chromosomal gyrA and/or parC mutations. Plasmid-mediated quinolone resistance genes were ubiquitous, with qnrB and aac(6')-Ib-cr being the most prevalent. Mutated LexA binding sites were found in all qnrB1 genes, and truncated qnrB pseudogenes were found in the majority of Citrobacter isolates.

High prevalence of multidrug resistant Enterobacteriaceae isolated from outpatient urine samples but not the hospital environment in Bo, Sierra Leone.

BACKGROUND: The rising level of antimicrobial resistance among bacterial pathogens is one of the most significant public health problems globally. While the antibiotic resistance of clinically important bacteria is closely tracked in many developed countries, the types and levels of resistance and multidrug resistance (MDR) among pathogens currently circulating in most countries of sub-Saharan Africa are virtually unknown. METHODS: From December 2013 to April 2014, we collected 93 urine specimens from all outpatients showing symptoms of urinary tract infection (UTI) and 189 fomite swabs from a small hospital in Bo, Sierra Leone. Culture on chromogenic agar combined with biochemical and DNA sequence-based assays was used to detect and identify the bacterial isolates. Their antimicrobial susceptibilities were determined using a panel of 11 antibiotics or antibiotic combinations. RESULTS: The 70 Enterobacteriaceae urine isolates were identified as Citrobacter freundii (n = 22), Klebsiella pneumoniae (n = 15), Enterobacter cloacae (n = 15), Escherichia coli (n = 13), Enterobacter sp./Leclercia sp. (n = 4) and Escherichia hermannii (n = 1). Antimicrobial susceptibility testing demonstrated that 85.7 % of these isolates were MDR while 64.3 % produced an extended-spectrum ß-lactamase (ESBL). The most notable observations included widespread resistance to sulphonamides (91.4 %), chloramphenicol (72.9 %), gentamycin (72.9 %), ampicillin with sulbactam (51.4 %) and ciprofloxacin (47.1 %) with C. freundii exhibiting the highest and E. coli the lowest prevalence of multidrug resistance. The environmental cultures resulted in only five Enterobacteriaceae isolates out of 189 collected with lower overall antibiotic resistance. CONCLUSIONS: The surprisingly high proportion of C. freundii found in urine of patients with suspected UTI supports earlier findings of the growing role of this pathogen in UTIs in low-resource countries. The isolates of all analyzed species showed worryingly high levels of resistance to both first- and second-line antibiotics as well as a high frequency of MDR and ESBL phenotypes, which likely resulted from the lack of consistent antibiotic stewardship policies in Sierra Leone. Analysis of hospital environmental isolates however suggested that fomites in this naturally ventilated hospital were not a major reservoir for Enterobacteriaceae or antibiotic resistance determinants.

Sequence variability and geographic distribution of Lassa virus, Sierra Leone.

Lassa virus (LASV) is endemic to parts of West Africa and causes highly fatal hemorrhagic fever. The multimammate rat (Mastomys natalensis) is the only known reservoir of LASV. Most human infections result from zoonotic transmission. The very diverse LASV genome has 4 major lineages associated with different geographic locations. We used reverse transcription PCR and resequencing microarrays to detect LASV in 41 of 214 samples from rodents captured at 8 locations in Sierra Leone. Phylogenetic analysis of partial sequences of nucleoprotein (NP), glycoprotein precursor (GPC), and polymerase (L) genes showed 5 separate clades within lineage IV of LASV in this country. The sequence diversity was higher than previously observed; mean diversity was 7.01% for nucleoprotein gene at the nucleotide level. These results may have major implications for designing diagnostic tests and therapeutic agents for LASV infections in Sierra Leone.

Use of the FilmArray System for Detection of Zaire ebolavirus in a Small Hospital in Bo, Sierra Leone.

Laboratories associated with small hospitals often have limited expertise, personnel, and equipment to rapidly identify rare and emerging infectious diseases. We describe the successful use of the FilmArray system for rapid detection of Ebola virus directly from clinical samples in 6 out of 83 tested subjects in a small health care center in Sierra Leone.

Child bed net use before, during, and after a bed net distribution campaign in Bo, Sierra Leone.

BACKGROUND: This analysis examined how the proportion of children less than 5-years-old who slept under a bed net the previous night changed during and after a national long-lasting insecticidal net (LLIN) distribution campaign in Sierra Leone in November-December 2010. METHODS: A citywide cross-sectional study in 2010-2011 interviewed the caregivers of more than 3000 under-five children from across urban Bo, Sierra Leone. Chi squared tests were used to assess change in use rates over time, and multivariate regression models were used to examine the factors associated with bed net use. RESULTS: Reported rates of last-night bed net use changed from 38.7 % (504/1304) in the months before the LLIN campaign to 21.8 % (78/357) during the week of the campaign to 75.3 % (1045/1387) in the months after the national campaign. The bed net use rate significantly increased (p < 0.01) from before the campaign to after the universal LLIN distribution campaign in all demographic, socioeconomic, and health behaviour groups, even though reported use during the campaign dropped significantly. CONCLUSION: Future malaria prevention efforts will need to promote consistent use of LLINs and address any remaining disparities in insecticide-treated bed net (ITN) use.

Attitudes toward home-based malaria testing in rural and urban Sierra Leone.

BACKGROUND: The purpose of this study was to examine malaria testing practices and preferences in Bo, Sierra Leone, and to ascertain interest in and willingness to take a home-based rapid diagnostic test administered by a community health volunteer (CHV) or a trained family member rather than travelling to a clinical facility for laboratory-based testing. METHODS: A population-based, cross-sectional survey of 667 randomly-sampled rural households and 157 urban households was conducted in December 2013 and January 2014. RESULTS: Among rural residents, 69% preferred a self/family- or CHV-conducted home-based malaria test and 20% preferred a laboratory-based test (with others indicating no preference). Among urban residents, these numbers were 38% and 44%, respectively. If offered a home-based test, 28% of rural residents would prefer a self/family-conducted test and 68% would prefer a CHV-assisted test. For urban residents, these numbers were 21% and 77%. In total, 36% of rural and 63% of urban residents reported usually taking a diagnostic test to confirm suspected malaria. The most common reasons for not seeking malaria testing were the cost of testing, waiting to see if the fever resolved on its own, and not wanting to travel to a clinical facility for a test. In total, 32% of rural and 27% of urban participants were very confident they could perform a malaria test on themselves or a family member without assistance, 50% of rural and 62% of urban participants were very confident they could perform a test after training, and 56% of rural and 33% of urban participants said they would pay more for a home-based test than a laboratory-based test. CONCLUSION: Expanding community case management of malaria to include home testing by CHVs and family members may increase the proportion of individuals with febrile illnesses who confirm a positive diagnosis prior to initiating treatment.

Syndromic surveillance of peste des petits ruminants and other animal diseases in Koinadugu district, Sierra Leone, 2011-2012.

PURPOSE: The purpose of this study was to conduct syndromic surveillance for important veterinary diseases in Koinadugu district, Northern Province, Sierra Leone. METHODS: This study examined all veterinary syndromic surveillance reports submitted to the district veterinary office from January 2011 through December 2012. RESULTS: In total, 5679 case reports were submitted, including 2394 fatalities. The most common syndrome reported was consistent with peste de petits ruminants (PPR) in goats (n = 1649). PPR cases were reported from eight of 11 chiefdoms in the district, with a 42 per 1000 reported incidence rate and a 48 % case fatality rate. Other syndromes reported were consistent with trypanosomiasis in cattle (n = 1402), Newcastle disease in poultry (n = 911), black quarter in cattle (n = 691), and haemorrhagic septicaemia in cattle (n = 542). CONCLUSIONS: Expanded use of the PPR virus vaccine may be required to help control the spread of the infection. Improved community-based prevention efforts may be effective for better control of trypanosomiasis and all these conditions.