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  • Paediatric Buruli ulcer in Australia

    Walker, G; Friedman, D; Cooper, C; O'Brien, M; McDonald, A; Callan, P; O'Brien, D; MSF UK Manson Unit (2019-12-10)
    AIM: This study describes an Australian cohort of paediatric Buruli ulcer (BU) patients and compares them with adult BU patients. METHODS: Analysis of a prospective cohort of all BU cases managed at Barwon Health, Victoria, from 1 January 1998 to 31 May 2018 was performed. Children were defined as ≤15 years of age. RESULTS: A total of 565 patients were included: 52 (9.2%) children, 289 (51.2%) adults aged 16-64 years and 224 (39.6%) adults aged ≥65 years. Among children, half were female and the median age was 8.0 years (interquartile range 4.8-12.3 years). Six (11.5%) cases were diagnosed from 2001 to 2006, 14 (26.9%) from 2007 to 2012 and 32 (61.5%) from 2013 to 2018. Compared to adults, children had a significantly higher proportion of non-ulcerative lesions (32.7%, P < 0.001) and a higher proportion of severe lesions (26.9%, P < 0.01). The median duration of symptoms prior to diagnosis was shorter for children compared with adults aged 16-64 years (42 vs. 56 days, P = 0.04). Children were significantly less likely to experience antibiotic complications (6.1%) compared with adults (20.6%, P < 0.001), but had a significantly higher rate of paradoxical reactions (38.8%) compared with adults aged 16-64 (19.2%) (P < 0.001). Paradoxical reactions in children occurred significantly earlier than in adults (median 17 vs. 56 days, P < 0.01). Cure rates were similarly high for children compared to adults treated with antibiotics alone or with antibiotics and surgery. CONCLUSIONS: Paediatric BU cases in Australia are increasing and represent an important but stable proportion of Australian BU cohorts. Compared with adults, there are significant differences in clinical presentation and treatment outcomes.
  • Increased risk of acquisition and transmission of ESBL-producing Enterobacteriaceae in malnourished children exposed to amoxicillin

    Maataoui, N; Langendorf, C; Berthe, F; Grais, R; van Schaik, W; Isanaka, S; Clermont, O; Bayjanov, J; Andremont, A; Armand-Lefevre, Laurence; et al. (Oxford University Press (OUP) We regret that this article is behind a paywall., 2019-12-10)
    OBJECTIVES: Routine amoxicillin for children with uncomplicated severe acute malnutrition raises concerns of increasing antibiotic resistance. We performed an ancillary study nested within a double-blind, placebo-controlled trial in Niger testing the role of routine 7 day amoxicillin therapy in nutritional recovery of children 6 to 59 months of age with uncomplicated severe acute malnutrition. METHODS: We screened 472 children for rectal carriage of ESBL-producing Enterobacteriaceae (ESBL-E) as well as their household siblings under 5 years old, at baseline and Week 1 (W1) and Week 4 (W4) after start of therapy, and characterized strains by WGS. ClinicalTrials.gov: NCT01613547. RESULTS: Carriage in index children at baseline was similar in the amoxicillin and the placebo groups (33.8% versus 27.9%, P = 0.17). However, acquisition of ESBL-E in index children at W1 was higher in the amoxicillin group than in the placebo group (53.7% versus 32.2%, adjusted risk ratio = 2.29, P = 0.001). Among 209 index and sibling households possibly exposed to ESBL-E transmission, 16 (7.7%) had paired strains differing by ≤10 SNPs, suggesting a high probability of transmission. This was more frequent in households from the amoxicillin group than from the placebo group [11.5% (12/104) versus 3.8% (4/105), P = 0.04]. CONCLUSIONS: Among children exposed to amoxicillin, ESBL-E colonization was more frequent and the risk of transmission to siblings higher. Routine amoxicillin should be carefully balanced with the risks associated with ESBL-E colonization.
  • A systematic review of the epidemiology of human monkeypox outbreaks and implications for outbreak strategy.

    Beer, EN; Rao, VB (The Public Library of Science, 2019-10-16)
    Monkeypox is a vesicular-pustular illness that carries a secondary attack rate in the order of 10% in contacts unvaccinated against smallpox. Case fatality rates range from 1 to 11%, but scarring and other sequelae are common in survivors. It continues to cause outbreaks in remote populations in Central and West Africa, in areas with poor access and weakened or disrupted surveillance capacity and information networks. Recent outbreaks in Nigeria (2017-18) and Cameroon (2018) have occurred where monkeypox has not been reported for over 20 years. This has prompted concerns over whether there have been changes in the biology and epidemiology of the disease that may in turn have implications for how outbreaks and cases should best be managed. A systematic review was carried out to examine reported data on human monkeypox outbreaks over time, and to identify if and how epidemiology has changed. Published and grey literature were critically analysed, and data extracted to inform recommendations on outbreak response, use of case definitions and public health advice. The level of detail, validity of data, geographical coverage and consistency of reporting varied considerably across the 71 monkeypox outbreak documents obtained. An increase in cases reported over time was supported by literature from the Democratic Republic of Congo (DRC). Data were insufficient to measure trends in secondary attack rates and case fatality rates. Phylogenetic analyses consistently identify two strains of the virus without evidence of emergence of a new strain. Understanding of monkeypox virulence with regard to clinical presentation by strain is minimal, with infrequent sample collection and laboratory analysis. A variety of clinical and surveillance case definitions are described in the literature: two definitions have been formally evaluated and showed high sensitivity but low specificity. These were specific to a Congo-Basin (CB) strain-affected area of the DRC where they were used. Evidence on use of antibiotics for prophylaxis against secondary cutaneous infection is anecdotal and limited. Current evidence suggests there has been an increase in total monkeypox cases reported by year in the DRC irrespective of advancements in the national Integrated Disease Surveillance and Response (IDSR) system. There has been a marked increase in number of individual monkeypox outbreak reports, from outside the DRC in between 2010 and 2018, particularly in the Central African Republic (CAR) although this does not necessarily indicate an increase in annual cases over time in these areas. The geographical pattern reported in the Nigeria outbreak suggests a possible new and widespread zoonotic reservoir requiring further investigation and research. With regards to outbreak response, increased attention is warranted for high-risk patient groups, and nosocomial transmission risks. The animal reservoir remains unknown and there is a dearth of literature informing case management and successful outbreak response strategies. Up-to-date complete, consistent and longer-term research is sorely needed to inform and guide evidence-based response and management of monkeypox outbreaks.
  • Snakebite and snake identification: empowering neglected communities and health-care providers with AI

    De Castaneda, RR; Durso, AM; Ray, N; Fernandez, JL; Williams, DJ; Alcoba, G; Chappuis, F; Salathe, M; Bolon, I (Elsevier, 2019-09-01)
  • 'I treat it but I don't know what this disease is': a qualitative study on noma (cancrum oris) and traditional healing in northwest Nigeria.

    Farley, E; Bala, HM; Lenglet, A; Mehta, U; Abubakar, N; Samuel, J; de Jong, A; Bil, K; Oluyide, B; Fotso, A; et al. (Oxford University Press, 2019-08-24)
    BACKGROUND: Noma, a neglected disease mostly affecting children, with a 90% mortality rate if untreated, is an orofacial gangrene that disintegrates the tissues of the face in <1 wk. Noma can become inactive with early stage antibiotic treatment. Traditional healers, known as mai maganin gargajiya in Hausa, play an important role in the health system and provide care to noma patients. METHODS: We conducted 12 in-depth interviews with caretakers who were looking after noma patients admitted at the Noma Children's Hospital and 15 traditional healers in their home villages in Sokoto state, northwest Nigeria. We explored perceptions of noma, relationship dynamics, healthcare practices and intervention opportunities. Interviews were audiorecorded, transcribed and translated. Manual coding and thematic analysis were utilised. RESULTS: Traditional healers offered specialised forms of care for specific conditions and referral guidance. They viewed the stages of noma as different conditions with individualised remedies and were willing to refer noma patients. Caretakers trusted traditional healers. CONCLUSIONS: Traditional healers could play a crucial role in the early detection of noma and the health-seeking decision-making process of patients. Intervention programmes should include traditional healers through training and referral partnerships. This collaboration could save lives and reduce the severity of noma complications.
  • Quantifying the incidence of severe-febrile-illness hospital admissions in sub-Saharan Africa.

    Roddy, P; Dalrymple, U; Jensen, TO; Dittrich, S; Rao, VB; Pfeffer, DA; Twohig, KA; Roberts, T; Bernal, O; Guillen, E (Public Library of Science, 2019-07-25)
    Severe-febrile-illness (SFI) is a common cause of morbidity and mortality across sub-Saharan Africa (SSA). The burden of SFI in SSA is currently unknown and its estimation is fraught with challenges. This is due to a lack of diagnostic capacity for SFI in SSA, and thus a dearth of baseline data on the underlying etiology of SFI cases and scant SFI-specific causative-agent prevalence data. To highlight the public health significance of SFI in SSA, we developed a Bayesian model to quantify the incidence of SFI hospital admissions in SSA. Our estimates indicate a mean population-weighted SFI-inpatient-admission incidence rate of 18.4 (6.8-31.1, 68% CrI) per 1000 people for the year 2014, across all ages within areas of SSA with stable Plasmodium falciparum transmission. We further estimated a total of 16,200,337 (5,993,249-27,321,779, 68% CrI) SFI hospital admissions. This analysis reveals the significant burden of SFI in hospitals in SSA, but also highlights the paucity of pathogen-specific prevalence and incidence data for SFI in SSA. Future improvements in pathogen-specific diagnostics for causative agents of SFI will increase the abundance of SFI-specific prevalence and incidence data, aid future estimations of SFI burden, and enable clinicians to identify SFI-specific pathogens, administer appropriate treatment and management, and facilitate appropriate antibiotic use.
  • Hepatitis E should be considered a neglected tropical disease.

    Asman, AS; Ciglenecki, I; Wamala, JF; Lynch, J; Aggarwal, R; Rahman, M; Wong, S; Serafini, M; Moussa, AM; Dalton, HR; et al. (Public Library of Science, 2019-07-25)
  • . Deriving the optimal limit of detection for an HCV point-of-care test for viraemic infection: Analysis of a global dataset

    Freiman, JM; Wang, J; Easterbrook, PJ; Horsburgh, CR; Marinucci, F; White, LF; Kamkamidze, G; Krajden, M; Loarec, A; Njouom, R; et al. (Elsevier, 2019-07)
    Background & Aims Affordable point-of-care tests for hepatitis C (HCV) viraemia are needed to improve access to treatment in low- and middle-income countries. Our aims were to determine the target limit of detection (LOD) necessary to diagnose the majority of people with HCV eligible for treatment, and identify characteristics associated with low-level viraemia (LLV) (defined as the lowest 3% of the distribution of HCV RNA) to understand those at risk of being misdiagnosed. Methods We established a multi-country cross-sectional dataset of first available quantitative HCV RNA measurements linked to demographic and clinical data. We excluded individuals on HCV treatment. We analysed the distribution of HCV RNA and determined critical thresholds for detection of HCV viraemia. We then performed logistic regression to evaluate factors associated with LLV, and derived relative sensitivities for significant covariates. Results The dataset included 66,640 individuals with HCV viraemia from across the world. The LOD for the 95th and 99th percentiles were 3,311 IU/ml and 214 IU/ml. The LOD for the 97th percentile was 1,318 IU/ml (95% CI 1,298.4–1,322.3). Factors associated with LLV, defined as HCV RNA <1,318 IU/ml, were younger age 18–30 vs. 51–64 years (odds ratios [OR] 2.56; 95% CI 2.19–2.99), female vs. male sex (OR 1.32; 95% CI 1.18–1.49), and advanced fibrosis stage F4 vs. F0-1 (OR 1.44; 95% CI 1.21–1.69). Only the younger age group had a decreased relative sensitivity below 95%, at 93.3%. Conclusions In this global dataset, a test with an LOD of 1,318 IU/ml would identify 97% of viraemic HCV infections among almost all populations. This LOD will help guide manufacturers in the development of affordable point-of-care diagnostics to expand HCV testing and linkage to care in low- and middle-income countries. Lay summary We created and analysed a dataset from 12 countries with 66,640 participants with chronic hepatitis C virus infection. We determined that about 97% of those with viraemic infection had 1,300 IU/ml or more of circulating virus at the time of diagnosis. While current diagnostic tests can detect as little as 12 IU/ml of virus, our findings suggest that increasing the level of detection closer to 1,300 IU/ml would maintain good test accuracy and will likely enable development of more affordable portable tests for use in low- and middle-income countries.
  • Reviewing evidence of the clinical effectiveness of commercially available antivenoms in sub-Saharan Africa identifies the need for a multi-centre, multi-antivenom clinical trial

    Potet, J; Smith, J; McIver, L (Public Library of Science, 2019-06-24)
    BACKGROUND: Snakebite envenoming kills more than more than 20,000 people in Sub-Saharan Africa every year. Poorly regulated markets have been inundated with low-price, low-quality antivenoms. This review aimed to systematically collect and analyse the clinical data on all antivenom products now available in markets of sub-Saharan Africa. METHODOLOGY/PRINCIPAL FINDINGS: Our market analysis identified 12 polyspecific and 4 monospecific antivenom products in African markets. Our search strategy was first based on a systematic search of publication databases, followed by manual searches and discussions with experts. All types of data, including programmatic data, were eligible. All types of publications were eligible, including grey literature. Cohorts of less than 10 patients were excluded. 26 publications met the inclusion criteria. Many publications had to be excluded because clinical outcomes were not clearly linked to a specific product. Our narrative summaries present product-specific clinical data in terms of safety and effectiveness against the different species and envenoming syndromes. Three products (EchiTabPlus, EchiTabG, SAIMR-Echis-monovalent) were found to have been tested in robust clinical studies and found effective against envenoming caused by the West African carpet viper (Echis ocellatus). Four products (Inoserp-Panafricain, Fav-Afrique, SAIMR-Polyvalent, Antivipmyn-Africa) were found to have been evaluated only in observational single-arm studies, with varying results. For nine other products, there are either no data in the public domain, or only negative data suggesting a lack of effectiveness. CONCLUSIONS/SIGNIFICANCE: Clinical data vary among the different antivenom products currently in African markets. Some products are available commercially although they have been found to lack effectiveness. The World Health Organization should strengthen its capacity to assess antivenom products, support antivenom manufacturers, and assist African countries and international aid organizations in selecting appropriate quality antivenoms.
  • Tungiasis: a highly neglected disease among neglected diseases. Case series from Nduta refugee camp (Tanzania).

    Najera Villagrana, SM; Garcia Naranjo Santisteban, A (Oxford University Press, 2019-06-24)
    Tungiasis is a highly prevalent yet neglected disease of populations affected by extreme poverty. It causes great discomfort and pain, leads to social stigmatization and, when left untreated, can cause serious complications. Although natural repellents have been shown to be effective, too little is being done in terms of systematic prevention and treatment. In addition, self-treatment (usually extraction of fleas with non-sterile sharp instruments) comports high risks of infection, notably with viral hepatitis and human immunodeficiency virus. In this article, we report seven severe cases of tungiasis in children living in a refugee camp in Tanzania, all of whom were treated with surgical extraction of the fleas because the topical treatment (dimethicone) was not available. Refugee camps-particularly in sub-Saharan Africa where tungiasis is endemic-should be considered high-risk areas for the condition. Aid organizations should engage in active case searching, and health promotion should be systematically carried out.
  • Congo’s Ebola epidemic—a failed response and the need for a reset

    Huster, K; Healy, J (BMJ Publishing Group, 2019-05-24)
  • Molecular epidemiology of hepatitis C virus in Cambodia during 2016-2017.

    Nouhin, J; Iwamoto, M; Prak, S; Dousset, JP; Phon, K; Heng, S; Kerleguer, A; Le Paih, M; Dussart, P; Maman, D; et al. (Nature Publishing Group, 2019-05-13)
    In Cambodia, little epidemiological data of hepatitis C virus (HCV) is available. All previous studies were limited to only small or specific populations. In the present study, we performed a characterization of HCV genetic diversity based on demography, clinical data, and phylogenetic analysis of HCV non-structural 5B (NS5B) sequences belonging to a large cohort of patients (n = 3,133) coming from majority part of Cambodia between September 2016 and December 2017. The phylogenetic analysis revealed that HCV genotype 1 and 6 were the most predominant and sharing equal proportions (46%). The remaining genotypes were genotype 2 (4.3%) and unclassified variants (3.6%). Among genotype 1, subtype 1b was the most prevalent subtype accounting for 94%. Within genotype 6, we observed a high degree of diversity and the most common viral subtypes were 6e (44%) and 6r (23%). This characteristic points to the longstanding history of HCV in Cambodia. Geographic specificity of viral genotype was not observed. Risks of HCV infection were mainly associated with experience of an invasive medical procedure (64.7%), having partner with HCV (19.5%), and blood transfusion (9.9%). In addition, all of these factors were comparable among different HCV genotypes. All these features define the specificity of HCV epidemiology in Cambodia.
  • Antibiotic resistance in conflict settings: lessons learned in the Middle East

    Kanapathipillai, R; Malou, N; Hopman, J; Bowman, C; Yousef, N; Michel, J; Hussein, N; Herard, P; Ousley, J; Mills, C; et al. (Oxford University Press, 2019-04-10)
    Me´decins Sans Frontie`res (MSF) has designed context-adapted antibiotic resistance (ABR) responses in countries across the Middle East. There, some health systems have been severely damaged by conflict resulting in delayed access to care, crowded facilities and supply shortages. Microbiological surveillance data are rarely available, but when MSF laboratories are installed we often find MDR bacteria at alarming levels.1 In MSF’s regional hospital in Jordan, where surgical patients have often had multiple surgeries in field hospitals before reaching definitive care (often four or more), MSF microbiological data analysis reveals that, among Enterobacteriaceae isolates, third-generation cephalosporin and carbapenem resistance is 86.2% and 4.3%, respectively; MRSA prevalence among Staphylococcus aureus is 60.5%; and resistance types and rates are similar in patients originating from Yemen, Syria and Iraq.1–3 These trends compel MSF to aggressively prevent and diagnose ABR in Jordan, providing ABR lessons that inform the antibiotic choices, microbiological diagnostics and anti-ABR strategies in other Middle Eastern MSF trauma projects (such as Yemen and Gaza). As a result, MSF has created a multifaceted, context-adapted, field experience-based, approach to ABR in hospitals in Middle Eastern conflict settings. We focus on three pillars: (1) infection prevention and control (IPC); (2) microbiology and surveillance; and (3) antibiotic stewardship.
  • An Epidemic of Suspicion - Ebola and Violence in the DRC

    Nguyen, VK (Massachusetts Medical Society, 2019-04-04)
    Until the 2014 Ebola epidemic in West Africa, Ebola outbreaks had been sporadic, small, and largely confined to isolated rural villages in Central Africa. But the 2014 epidemic broke all the rules and killed more than 15,000 people; since then, more outbreaks have been reaching larger urban centers, sometimes resulting in uncontrolled spread. The current epidemic in the Democratic Republic of Congo (DRC) has triggered a massive international response, which has been met by violence, culminating in attacks at the end of February that partially destroyed Ebola treatment units in the regional hub of Butembo and its township, Katwa. This area is the epicenter of the epidemic, which is likely to be fueled by any breakdown of isolation and treatment efforts.
  • 2017 Outbreak of Ebola Virus Disease in Northern Democratic Republic of Congo

    Nsio, J; Kapetshi, J; Makiala, S; Raymond, F; Tshapenda, G; Boucher, N; Corbeil, J; Okitandjate, A; Mbuyi, G; Kiyele, M; et al. (Oxford University Press, 2019-04-03)
    Background In 2017, the Democratic Republic of the Congo (DRC) recorded its eighth Ebola virus disease (EVD) outbreak, approximately 3 years after the previous outbreak. Methods Suspect cases of EVD were identified on the basis of clinical and epidemiological information. Reverse transcription–polymerase chain reaction (RT-PCR) analysis or serological testing was used to confirm Ebola virus infection in suspected cases. The causative virus was later sequenced from a RT-PCR–positive individual and assessed using phylogenetic analysis. Results Three probable and 5 laboratory-confirmed cases of EVD were recorded between 27 March and 1 July 2017 in the DRC. Fifty percent of cases died from the infection. EVD cases were detected in 4 separate areas, resulting in > 270 contacts monitored. The complete genome of the causative agent, a variant from the Zaireebolavirus species, denoted Ebola virus Muyembe, was obtained using next-generation sequencing. This variant is genetically closest, with 98.73% homology, to the Ebola virus Mayinga variant isolated from the first DRC outbreaks in 1976–1977. Conclusion A single spillover event into the human population is responsible for this DRC outbreak. Human-to-human transmission resulted in limited dissemination of the causative agent, a novel Ebola virus variant closely related to the initial Mayinga variant isolated in 1976–1977 in the DRC.
  • Antibiotic Resistance in Pacific Island Countries and Territories: A Systematic Scoping Review

    Foxlee, ND; Townell, N; McIver, L; Lau, CL (Multidisciplinary Digital Publishing Institute, 2019-03-19)
    Several studies have investigated antimicrobial resistance in low- and middle-income countries, but to date little attention has been paid to the Pacific Islands Countries and Territories (PICTs). This study aims to review the literature on antibiotic resistance (ABR) in healthcare settings in PICTs to inform further research and future policy development for the region. Following the PRISMA-ScR checklist health databases and grey literature sources were searched. Three reviewers independently screened the literature for inclusion, data was extracted using a charting tool and the results were described and synthesised. Sixty-five studies about ABR in PICTs were identified and these are primarily about New Caledonia, Fiji and Papua New Guinea. Ten PICTs contributed the remaining 21 studies and nine PICTs were not represented. The predominant gram-positive pathogen reported was community-acquired methicillin resistant S. aureus and the rates of resistance ranged widely (>50% to <20%). Resistance reported in gram-negative pathogens was mainly associated with healthcare-associated infections (HCAIs). Extended spectrum beta-lactamase (ESBL) producing K. pneumoniae isolates were reported in New Caledonia (3.4%) and Fiji (22%) and carbapenem resistant A. baumannii (CR-ab) isolates in the French Territories (24.8%). ABR is a problem in the PICTs, but the epidemiology requires further characterisation. Action on strengthening surveillance in PICTs needs to be prioritised so strategies to contain ABR can be fully realised.
  • Real-time analysis of the diphtheria outbreak in forcibly displaced Myanmar nationals in Bangladesh

    Finger, F; Funk, S; White, K; Siddiqui, MR; Edmunds, WJ; Kucharski, AJ (2019-03-12)
    Between August and December 2017, more than 625,000 Rohingya from Myanmar fled into Bangladesh, settling in informal makeshift camps in Cox’s Bazar district and joining 212,000 Rohingya already present. In early November, a diphtheria outbreak hit the camps, with 440 reported cases during the first month. A rise in cases during early December led to a collaboration between teams from Médecins sans Frontières—who were running a provisional diphtheria treatment centre—and the London School of Hygiene and Tropical Medicine with the goal to use transmission dynamic models to forecast the potential scale of the outbreak and the resulting resource needs. Methods We first adjusted for delays between symptom onset and case presentation using the observed distribution of reporting delays from previously reported cases. We then fit a compartmental transmission model to the adjusted incidence stratified by age group and location. Model forecasts with a lead time of 2 weeks were issued on 12, 20, 26 and 30 December and communicated to decision-makers. Results The first forecast estimated that the outbreak would peak on 19 December in Balukhali camp with 303 (95% posterior predictive interval 122–599) cases and would continue to grow in Kutupalong camp, requiring a bed capacity of 316 (95% posterior predictive interval (PPI) 197–499). On 19 December, a total of 54 cases were reported, lower than forecasted. Subsequent forecasts were more accurate: on 20 December, we predicted a total of 912 cases (95% PPI 367–2183) and 136 (95% PPI 55–327) hospitalizations until the end of the year, with 616 cases actually reported during this period. Conclusions Real-time modelling enabled feedback of key information about the potential scale of the epidemic, resource needs and mechanisms of transmission to decision-makers at a time when this information was largely unknown. By 20 December, the model generated reliable forecasts and helped support decision-making on operational aspects of the outbreak response, such as hospital bed and staff needs, and with advocacy for control measures. Although modelling is only one component of the evidence base for decision-making in outbreak situations, suitable analysis and forecasting techniques can be used to gain insights into an ongoing outbreak.
  • Clinical Practice Guidelines for Chagas Disease: Recent Developments and Future Needs

    Forsyth, C; Marchiol, A; Herazo, R; Chatelain, E; Batista, C; Strub-Wourgraft, N; Bilbe, G; Sosa-Estani, S (Brazilian Society of Tropical Medicine, 2019-03-08)
  • Control of Ebola virus disease outbreaks: Comparison of health care worker-targeted and community vaccination strategies.

    Robert, A; Camacho, A; Edmunds, WJ; Rosello A; Baguelin, M; Muyembe, JJT; Eggo, RM; Keita, S (Elsevier, 2019-03-02)
    Health care workers (HCW) are at risk of infection during Ebola virus disease outbreaks and therefore may be targeted for vaccination before or during outbreaks. The effect of these strategies depends on the role of HCW in transmission which is understudied. To evaluate the effect of HCW-targeted or community vaccination strategies, we used a transmission model to explore the relative contribution of HCW and the community to transmission. We calibrated the model to data from multiple Ebola outbreaks. We quantified the impact of ahead-of-time HCW-targeted strategies, and reactive HCW and community vaccination. We found that for some outbreaks (we call "type 1″) HCW amplified transmission both to other HCW and the community, and in these outbreaks prophylactic vaccination of HCW decreased outbreak size. Reactive vaccination strategies had little effect because type 1 outbreaks ended quickly. However, in outbreaks with longer time courses ("type 2 outbreaks"), reactive community vaccination decreased the number of cases, with or without prophylactic HCW-targeted vaccination. For both outbreak types, we found that ahead-of-time HCW-targeted strategies had an impact at coverage of 30%. The vaccine strategies tested had a different impact depending on the transmission dynamics and previous control measures. Although we will not know the characteristics of a new outbreak, ahead-of-time HCW-targeted vaccination can decrease the total outbreak size, even at low vaccine coverage.
  • Diagnostics for filovirus detection: impact of recent outbreaks on the diagnostic landscape

    Emperador DM; Mazzola LT; Trainor BW; Chua A; Kelly-Cirino C (BMJ Publishing Group, 2019-02-07)
    Ebolaviruses and Marburg virus (MARV) both belong to the family Filoviridae and cause severe haemorrhagic fever in humans. Due to high mortality rates and potential for spread from rural to urban regions, they are listed on the WHO R&D blueprint of high-priority pathogens. Recent ebolavirus outbreaks in Western and Central Africa have highlighted the importance of diagnostic testing in epidemic preparedness for these pathogens and led to the rapid development of a number of commercially available benchtop and point-of-care nucleic acid amplification tests as well as serological assays and rapid diagnostic tests. Despite these advancements, challenges still remain. While products approved under emergency use licenses during outbreak periods may continue to be used post-outbreak, a lack of clarity and incentive surrounding the regulatory approval pathway during non-outbreak periods has deterred many manufacturers from seeking full approvals. Waning of funding and poor access to samples after the 2014–2016 outbreak also contributed to cessation of development once the outbreak was declared over. There is a need for tests with improved sensitivity and specificity, and assays that can use alternative sample types could reduce the need for invasive procedures and expensive equipment, making testing in field conditions more feasible. For MARV, availability of diagnostic tests is still limited, restricted to a single ELISA test and assay panels designed to differentiate between multiple pathogens. It may be helpful to extend the target product profile for ebolavirus diagnostics to include MARV, as the viruses have many overlapping characteristics.

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