To see all articles in this section, click on "browse by Title".

Recent Submissions

  • Dengue in Western Uganda: a prospective cohort of children presenting with undifferentiated febrile illness

    Boyce, RM; Collins, M; Muhindo, R; Nakakande, R; Ciccone, EJ; Grounds, S; Espinoza, D; Zhu, Y; Matte, M; Ntaro, M; et al. (BMC, 2020-11-11)
    Background The spatial distribution and burden of dengue in sub-Saharan Africa remains highly uncertain, despite high levels of ecological suitability. The goal of this study was to describe the epidemiology of dengue among a cohort of febrile children presenting to outpatient facilities located in areas of western Uganda with differing levels of urbanicity and malaria transmission intensity. Methods Eligible children were first screened for malaria using rapid diagnostic tests. Children with a negative malaria result were tested for dengue using a combination NS1/IgM/IgG rapid test (SD Bioline Dengue Duo). Confirmatory testing by RT-PCR was performed in a subset of participants. Antigen-capture ELISA was performed to estimate seroprevalence. Results Only 6 of 1416 (0.42%) children had a positive dengue rapid test, while none of the RT-PCR results were positive. ELISA testing demonstrated reactive IgG antibodies in 28 (2.2%) participants with the highest prevalence seen at the urban site in Mbarara (19 of 392, 4.9%, p < 0.001). Conclusions Overall, these findings suggest that dengue, while present, is an uncommon cause of non-malarial, pediatric febrile illness in western Uganda. Further investigation into the eocological factors that sustain low-level transmission in urban settings are urgently needed to reduce the risk of epidemics.
  • Point-of-Care Approaches for Meningitis Diagnosis in a Low-Resource Setting (Southwestern Uganda): Observational Cohort Study Protocol of the “PI-POC” Trial

    Gaudenzi, G; Kumbakumba, E; Rasti, R; Nanjebe, D; Reu, P; Nyehangane, D; Martensson, A; Nassejje, M; Karlsson, J; Mzee, J; et al. (JMIR Publications, 2020-11-04)
    Background: A timely differential diagnostic is essential to identify the etiology of central nervous system (CNS) infections in children, in order to facilitate targeted treatment, manage patients, and improve clinical outcome. Objective: The Pediatric Infection-Point-of-Care (PI-POC) trial is investigating novel methods to improve and strengthen the differential diagnostics of suspected childhood CNS infections in low-income health systems such as those in Southwestern Uganda. This will be achieved by evaluating (1) a novel DNA-based diagnostic assay for CNS infections, (2) a commercially available multiplex PCR-based meningitis/encephalitis (ME) panel for clinical use in a facility-limited laboratory setting, (3) proteomics profiling of blood from children with severe CNS infection as compared to outpatient controls with fever yet not severely ill, and (4) Myxovirus resistance protein A (MxA) as a biomarker in blood for viral CNS infection. Further changes in the etiology of childhood CNS infections after the introduction of the pneumococcal conjugate vaccine against Streptococcus pneumoniae will be investigated. In addition, the carriage and invasive rate of Neisseria meningitidis will be recorded and serotyped, and the expression of its major virulence factor (polysaccharide capsule) will be investigated. Methods: The PI-POC trial is a prospective observational study of children including newborns up to 12 years of age with clinical features of CNS infection, and age-/sex-matched outpatient controls with fever yet not severely ill. Participants are recruited at 2 Pediatric clinics in Mbarara, Uganda. Cerebrospinal fluid (for cases only), blood, and nasopharyngeal (NP) swabs (for both cases and controls) sampled at both clinics are analyzed at the Epicentre Research Laboratory through gold-standard methods for CNS infection diagnosis (microscopy, biochemistry, and culture) and a commercially available ME panel for multiplex PCR analyses of the cerebrospinal fluid. An additional blood sample from cases is collected on day 3 after admission. After initial clinical analyses in Mbarara, samples will be transported to Stockholm, Sweden for (1) validation analyses of a novel nucleic acid–based POC test, (2) biomarker research, and (3) serotyping and molecular characterization of S. pneumoniae and N. meningitidis. Results: A pilot study was performed from January to April 2019. The PI-POC trial enrollment of patients begun in April 2019 and will continue until September 2020, to include up to 300 cases and controls. Preliminary results from the PI-POC study are expected by the end of 2020. Conclusions: The findings from the PI-POC study can potentially facilitate rapid etiological diagnosis of CNS infections in low-resource settings and allow for novel methods for determination of the severity of CNS infection in such environment.
  • Cost-effectiveness of screening and treatment using direct-acting antivirals for chronic Hepatitis C virus in a primary care setting in Karachi, Pakistan

    Mafirakureva, N; Lim, AG; Khalid, GG; Aslam, K; Campbell, L; Zahid, H; Van den Bergh, R; Falq, G; Fortas, C; Wailly, Y; et al. (Wiley, 2020-10-14)
    abilistic sensitivity analyses (PSA). The ICER for implementing testing and treatment compared to no programme was US$450/DALY averted, with 100% of PSA runs falling below the per capita Gross Domestic Product threshold for cost-effective interventions for Pakistan (US$1,422). The ICER increased to US$532/DALY averted assuming national HCV seroprevalence (5.5% versus 33% observed in the intervention). If the cost of liver disease care was included (adapted from resource use data from Cambodia which has similar GDP to Pakistan), the ICER dropped to US$148/DALY, while it became cost-saving if a recently negotiated reduced drug cost of $75/treatment course was assumed (versus $282 in base-case) in addition to cost of liver disease care. In conclusion, screening and DAA treatment for HCV infection are expected to be highly cost-effective in Pakistan, supporting the expansion of similar screening and treatment programmes across Pakistan.
  • Outcomes of cholera and measles outbreak alerts in the Democratic Republic of Congo

    Makelele, JPK; Ade, S; Takarinda, KC; Manzi, M; Cuesta, JG; Acma, A; Yepez, MM; Mashak, M (International Union Against Tuberculosis and Lung Disease, 2020-09-21)
    Setting: In 1995, a rapid response project for humanitarian and medical emergencies, including outbreak responses, named ‘Pool d’Urgence Congo’ (PUC), was implemented in the Democratic Republic of Congo by Médecins Sans Frontières. Objective: To assess the outcomes of cholera and measles outbreak alerts that were received in the PUC surveillance system between 2016 and 2018. Design: This was a retrospective cross-sectional study. Results: Overall, 459 outbreak alerts were detected, respectively 69% and 31% for cholera and measles. Of these, 32% were actively detected and 68% passively detected. Most alerts (90%) required no intervention and 10% of alerts had an intervention. There were 25% investigations that were not carried out despite thresholds being met; 17% interventions were not performed, the main reported reason being PUC operational capacity was exceeded. Confirmed cholera and measles outbreaks that met an investigation threshold comprised respectively 90% and 76% of alerts; 59% of measles investigations were followed by a delayed outbreak response of 14 days (n = 10 outbreaks). Conclusion: Some alerts for cholera and measles outbreaks that were detected in the PUC system did not lead to a response even when required; the main reported reason was limited operational capacity to respond to all of them.
  • Outcomes at 18 mo of 37 noma (cancrum oris) cases surgically treated at the Noma Children's Hospital, Sokoto, Nigeria.

    Farley, ES; Amirtharajah, M; Winters, RD; Taiwo, AO; Oyemakinda, MJ; Fosto, A; Torhee, LA; Mehta, UC; Bil, KA; Lenglet, AD (Oxford University Press, 2020-08-12)
    Background: Noma is a rapidly progressing infection of the oral cavity frequently resulting in severe facial disfigurement. We present a case series of noma patients surgically treated in northwest Nigeria. Methods: A retrospective analysis of routinely collected data (demographics, diagnosis and surgical procedures undergone) and in-person follow-up assessments (anthropometry, mouth opening and quality of life measurements) were conducted with patients who had surgery >6 mo prior to data collection. Results: Of the 37 patients included, 21 (56.8%) were male and 22 (62.9%) were aged >6 y. The median number of months between last surgery and follow-up was 18 (IQR 13, 25) mo. At admission, the most severely affected anatomical area was the outer cheek (n = 9; 36.0% of patients had lost between 26% and 50%). The most frequent surgical procedures were the deltopectoral flap (n = 16; 43.2%) and trismus release (n = 12; 32.4%). For the eight trismus-release patients where mouth opening was documented at admission, all had a mouth opening of 0-20 mm at follow-up. All patients reported that the surgery had improved their quality of life. Conclusions: Following their last surgical intervention, noma patients do experience some improvements in their quality of life, but debilitating long-term sequelae persist.
  • Hippopotamus bite morbidity: a report of 11 cases from Burundi.

    Haddara, MM; Haberisoni, JB; Trelles, M; Gohou, JP; Christella, K; Dominguez, L; Ali, E (Oxford University Press, 2020-08-10)
    Hippopotamus is one of the most-loved animals in Africa, yet it is aggressive and dangerous. The co-existence of humans in close proximity to their natural habitat increases the probability of human injury. Hippopotamus attacks have long been recognized to cause serious injuries, but its magnitude and burden are still unknown. The medical literature is very scarce when it comes to documenting hippopotamus bite injuries and their outcomes. We present a cohort of 11 patients who suffered hippopotamus bite injuries in Burundi. To our knowledge, this is the largest case series reporting on the clinical presentation, injury patterns and surgical outcomes of hippopotamus bites. The results show a high incidence of wound infections, amputations and permanent disability among other complications. Hippopotamus-inflicted injuries should, therefore, be triaged as major trauma rather than just 'mammalian bites'.
  • Painless: a case of congenital insensitivity to pain in a 5-year-old male

    Al Amroh, HH; Reyes, AL; Barret Austin Hillary, J; Al Khaffaf, WH (Oxford University Press, 2020-07-24)
    Background: several genetic disorders are known to be associated with congenital insensitivity to pain (CIP), a term often used to describe an impaired ability to perceive the type, intensity and quality of noxious stimuli. Children with CIP often injure themselves severely. The injury can go unnoticed or be misdiagnosed as child abuse because it is associated with multiple and recurrent injuries which may result in permanent damage. Patient findings: we report the case of a 5-year-old boy with a history of showing no signs of pain when exposed to accidental injuries such as trauma, burns or secondary chronic lesions. Conclusion: child abuse has a much higher occurrence rate than rare neuropathies such as the one we describe. However, CIP should be considered as a diagnosis in any child presenting with a history of poor or absent responses to painful stimuli.
  • Mandatory Notification of Chronic Chagas Disease: Confronting the Epidemiological Silence in the State of Goiás, Brazil

    da Rocha Siriano, L; Marchiol, A; Pereira Certo, M; Cubides, JC; Forsyth, C; Augusto de Sousa, F (MDPI, 2020-06-05)
    Objectives: This paper presents the results of the design and implementation process for the policy of compulsory notification of chronic Chagas disease in the Brazilian state of Goiás (Resolution No. 004/2013-GAB/SES-GO). Methods: The narrative was based on information provided by key actors that were part of the different stages of the process, built on contextual axes based on participants’ reflections about the establishment of the most accurate and coherent notification mechanisms. Results: The notification policy addressed the absence of historical data from patients in the state Chagas program, an increase in cases identified through serology, and weaknesses in vector control. Two key challenges involved human resources capacity and dissemination to public agencies and health care workers. Effective training and communication processes were key ingredients for successful implementation. Conclusions: The lack of public health measures aimed at the epidemiological surveillance of chronic Chagas cases constitutes a significant barrier for patients to access appropriate diagnosis, management and follow-up, and hampers the planning of necessary activities within health systems. The implementation of the notification policy in Goiás allows authorities to determine the real magnitude of Chagas disease in the population, so that an appropriate public health response can be mounted to meet the needs of affected people, thereby ending the epidemiological silence of Chagas disease.
  • Cost and cost-effectiveness of a simplified treatment model with direct-acting antivirals for chronic hepatitis C in Cambodia

    Walker, JG; Mafirakureva, N; Iwamoto, M; Campbell, L; Kim, CS; Hastings, RA; Doussett, JP; Le Paih, M; Balkan, S; Marquardt, T; et al. (Wiley, 2020-05-31)
    Background & aims: In 2016, Médecins Sans Frontières established the first general population Hepatitis C virus (HCV) screening and treatment site in Cambodia, offering free direct-acting antiviral (DAA) treatment. This study analysed the cost-effectiveness of this intervention. Methods: Costs, quality adjusted life years (QALYs) and cost-effectiveness of the intervention were projected with a Markov model over a lifetime horizon, discounted at 3%/year. Patient-level resource-use and outcome data, treatment costs, costs of HCV-related healthcare and EQ-5D-5L health states were collected from an observational cohort study evaluating the effectiveness of DAA treatment under full and simplified models of care compared to no treatment; other model parameters were derived from literature. Incremental cost-effectiveness ratios (cost/QALY gained) were compared to an opportunity cost-based willingness-to-pay threshold for Cambodia ($248/QALY). Results: The total cost of testing and treatment per patient for the full model of care was $925(IQR $668-1631), reducing to $376(IQR $344-422) for the simplified model of care. EQ-5D-5L values varied by fibrosis stage: decompensated cirrhosis had the lowest value, values increased during and following treatment. The simplified model of care was cost saving compared to no treatment, while the full model of care, although cost-effective compared to no treatment ($187/QALY), cost an additional $14 485/QALY compared to the simplified model, above the willingness-to-pay threshold for Cambodia. This result is robust to variation in parameters. Conclusions: The simplified model of care was cost saving compared to no treatment, emphasizing the importance of simplifying pathways of care for improving access to HCV treatment in low-resource settings. Keywords: Markov process; cost-effectiveness; direct-acting antiviral treatment; healthcare costs; hepatitis C; low-income population; treatment costs.
  • High sustained viral response rate in patients with hepatitis C using generic sofosbuvir and daclatasvir in Phnom Penh, Cambodia

    Zhang, M; O'Keefe, D; Iwamoto, M; Sann, K; Kien, A; Hang, V; Brucker, C; Jolivet, P; Ly, S; Chhit, D; et al. (Wiley, 2020-05-02)
    Safe and efficacious pan-genotypic direct-acting antiviral (DAA) regimens, such as sofosbuvir and daclatasvir (SOF+DCV)facilitate simplified models of care for hepatitis C virus (HCV). However, in Cambodia access to HCV testing and treatment has typically been low. In response, Médecins Sans Frontières(MSF) implemented a HCV testing and treatment pilot project in Phnom Penh, Cambodia in 2016. This project provides the first real-world evidence of SOF+DCV effectiveness across a large patient cohort using a simplified care model in Cambodia.Patients treated with SOF+DCV from September 2016 to June 2019 were included in the analysis. Medical standard operational procedures (SOPs) were simplified significantly across the study period. Treatment effectiveness was assessed by sustained viral response at 12 weeks post-treatment (SVR12) according to a modified intention to treat methodology. Treatment safety was assessed by clinical outcome and occurrence of serious and non-serious adverse events (S/AE). Of 9158 patients, median age was 57 years and 39.6% were male. At baseline assessment, 27.2% of patients had compensated cirrhosis and 2.9% had decompensated cirrhosis. Genotype 6 was predominant (53.0%). Among patients analysed according to modified intention to treat (n=8525), treatment effectiveness was high, with 97.2% of patients achieving SVR12. Occurrence of SAE was low (0.7%). Treatment effectiveness and safety was not affected by the iterative simplification to treatment modality. In conclusion, in this large treatment cohort in Phnom Penh, Cambodia, the SOF+DCV regimen showed high rates of treatment effectiveness and safety across patient sub-groups and during progressive simplification.
  • The prevalence of noma in northwest Nigeria

    Farley, E; Oyemakinde, MJ; Schuurmans, J; Ariti, C; Saleh, F; Uzoigwe, G; Bil, K; Oluyide, B; Fotso, A; Amirtharajah, M; et al. (BMJ, 2020-04-14)
    Background Noma, a rapidly progressing infection of the oral cavity, mainly affects children. The true burden is unknown. This study reports estimated noma prevalence in children in northwest Nigeria. Methods Oral screening was performed on all ≤15 year olds, with caretaker consent, in selected households during this cross-sectional survey. Noma stages were classified using WHO criteria and caretakers answered survey questions. The prevalence of noma was estimated stratified by age group (0–5 and 6–15 years). Factors associated with noma were estimated using logistic regression. Results A total of 177 clusters, 3499 households and 7122 children were included. In this sample, 4239 (59.8%) were 0–5 years and 3692 (52.1%) were female. Simple gingivitis was identified in 3.1% (n=181; 95% CI 2.6 to 3.8), acute necrotising gingivitis in 0.1% (n=10; CI 0.1 to 0.3) and oedema in 0.05% (n=3; CI 0.02 to 0.2). No cases of late-stage noma were detected. Multivariable analysis in the group aged 0–5 years showed having a well as the drinking water source (adjusted odds ratio (aOR) 2.1; CI 1.2 to 3.6) and being aged 3–5 years (aOR 3.9; CI 2.1 to 7.8) was associated with being a noma case. In 6–15 year olds, being male (aOR 1.5; CI 1.0 to 2.2) was associated with being a noma case and preparing pap once or more per week (aOR 0.4; CI 0.2 to 0.8) was associated with not having noma. We estimated that 129120 (CI 105294 to 1 52 947) individuals <15 years of age would have any stage of noma at the time of the survey within the two states. Most of these cases (93%; n=120 082) would be children with simple gingivitis. Conclusions Our study identified a high prevalence of children at risk of developing advanced noma. This disease is important but neglected and therefore merits inclusion in the WHO neglected tropical diseases list.
  • Managing COVID-19 in Low- and Middle-Income Countries

    Hopman, J; Allegranzi, B; Mehtar, S (American Medical Association, 2020-03-16)
  • Leaving no one behind: Towards equitable global elimination of hepatitis C

    Dahl, EH; Zahid, H; Aslam, K; Jafri, W (Edinburgh University Global Health Society, 2020-03-14)
  • Identifying the snake: First scoping review on practices of communities and healthcare providers confronted with snakebite across the world

    Bolon, I; Durso, A; Botero Mesa, S; Ray, N; Alcoba, G; Chappuis, F; Ruiz de Castañeda, R (Public Library of Science, 2020-03-05)
    BACKGROUND: Snakebite envenoming is a major global health problem that kills or disables half a million people in the world's poorest countries. Biting snake identification is key to understanding snakebite eco-epidemiology and optimizing its clinical management. The role of snakebite victims and healthcare providers in biting snake identification has not been studied globally. OBJECTIVE: This scoping review aims to identify and characterize the practices in biting snake identification across the globe. METHODS: Epidemiological studies of snakebite in humans that provide information on biting snake identification were systematically searched in Web of Science and Pubmed from inception to 2nd February 2019. This search was further extended by snowball search, hand searching literature reviews, and using Google Scholar. Two independent reviewers screened publications and charted the data. RESULTS: We analysed 150 publications reporting 33,827 snakebite cases across 35 countries. On average 70% of victims/bystanders spotted the snake responsible for the bite and 38% captured/killed it and brought it to the healthcare facility. This practice occurred in 30 countries with both fast-moving, active-foraging as well as more secretive snake species. Methods for identifying biting snakes included snake body examination, victim/bystander biting snake description, interpretation of clinical features, and laboratory tests. In nine publications, a picture of the biting snake was taken and examined by snake experts. Snakes were identified at the species/genus level in only 18,065/33,827 (53%) snakebite cases. 106 misidentifications led to inadequate victim management. The 8,885 biting snakes captured and identified were from 149 species including 71 (48%) non-venomous species. CONCLUSION: Snakebite victims and healthcare providers can play a central role in biting snake identification and novel approaches (e.g. photographing the snake, crowdsourcing) could help increase biting snake taxonomy collection to better understand snake ecology and snakebite epidemiology and ultimately improve snakebite management.
  • Effects and cost of different strategies to eliminate hepatitis C virus transmission in Pakistan: a modelling analysis

    Lim, AG; Walker, JG; Mafirakureva, N; Khalid, GG; Qureshi, H; Mahmood, H; Trickey, A; Fraser, H; Aslam, K; Falq, G; et al. (Elsevier, 2020-03-01)
    Background: The WHO elimination strategy for hepatitis C virus advocates scaling up screening and treatment to reduce global hepatitis C incidence by 80% by 2030, but little is known about how this reduction could be achieved and the costs of doing so. We aimed to evaluate the effects and cost of different strategies to scale up screening and treatment of hepatitis C in Pakistan and determine what is required to meet WHO elimination targets for incidence. Methods: We adapted a previous model of hepatitis C virus transmission, treatment, and disease progression for Pakistan, calibrating using available data to incorporate a detailed cascade of care for hepatitis C with cost data on diagnostics and hepatitis C treatment. We modelled the effect on various outcomes and costs of alternative scenarios for scaling up screening and hepatitis C treatment in 2018-30. We calibrated the model to country-level demographic data for 1960-2015 (including population growth) and to hepatitis C seroprevalence data from a national survey in 2007-08, surveys among people who inject drugs (PWID), and hepatitis C seroprevalence trends among blood donors. The cascade of care in our model begins with diagnosis of hepatitis C infection through antibody screening and RNA confirmation. Diagnosed individuals are then referred to care and started on treatment, which can result in a sustained virological response (effective cure). We report the median and 95% uncertainty interval (UI) from 1151 modelled runs. Findings: One-time screening of 90% of the 2018 population by 2030, with 80% referral to treatment, was projected to lead to 13·8 million (95% UI 13·4-14·1) individuals being screened and 350 000 (315 000-385 000) treatments started annually, decreasing hepatitis C incidence by 26·5% (22·5-30·7) over 2018-30. Prioritised screening of high prevalence groups (PWID and adults aged ≥30 years) and rescreening (annually for PWID, otherwise every 10 years) are likely to increase the number screened and treated by 46·8% and decrease incidence by 50·8% (95% UI 46·1-55·0). Decreasing hepatitis C incidence by 80% is estimated to require a doubling of the primary screening rate, increasing referral to 90%, rescreening the general population every 5 years, and re-engaging those lost to follow-up every 5 years. This approach could cost US$8·1 billion, reducing to $3·9 billion with lowest costs for diagnostic tests and drugs, including health-care savings, and implementing a simplified treatment algorithm. Interpretation: Pakistan will need to invest about 9·0% of its yearly health expenditure to enable sufficient scale up in screening and treatment to achieve the WHO hepatitis C elimination target of an 80% reduction in incidence by 2030.
  • Field challenges to measles elimination in the Democratic Republic of the Congo

    Coulborn, RM; Nackers, F; Bachy, C; Porten, K; Vochten, H; Ndele, E; Van Herp, M; Bibala-Faray, E; Cohuet, S; Panunzi, I (Elsevier, 2020-02-25)
    BACKGROUND: During a measles epidemic, the Ministry of Public Health (MOH) of the Democratic Republic of the Congo conducted supplementary immunization activities (2016-SIA) from August 28-September 3, 2016 throughout Maniema Province. From October 29-November 4, 2016, Médecins Sans Frontières and the MOH conducted a reactive measles vaccination campaign (2016-RVC) targeting children six months to 14 years old in seven health areas with heavy ongoing transmission despite inclusion in the 2016-SIA, and a post-vaccination survey. We report the measles vaccine coverage (VC) and effectiveness (VE) of the 2016-SIA and VC of the 2016-RVC. METHODS: A cross-sectional VC cluster survey stratified by semi-urban/rural health area and age was conducted. A retrospective cohort analysis of measles reported by the parent/guardian allowed calculation of the cumulative measles incidence according to vaccination status after the 2016-SIA for an estimation of crude and adjusted VE. RESULTS: In November 2016, 1145 children (6-59 months old) in the semi-urban and 1158 in the rural areas were surveyed. Post-2016-SIA VC (documentation/declaration) was 81.6% (95%CI: 76.5-85.7) in the semi-urban and 91.0% (95%CI: 84.9-94.7) in the rural areas. The reported measles incidence in October among children less than 5 years old was 5.0% for 2016-SIA-vaccinated and 11.2% for 2016-SIA-non-vaccinated in the semi-urban area, and 0.7% for 2016-SIA-vaccinated and 4.0% for 2016-SIA-non-vaccinated in the rural area. Post-2016-SIA VE (adjusted for age, sex) was 53.9% (95%CI: 2.9-78.8) in the semi-urban and 78.7% (95%CI: 0-97.1) in the rural areas. Post 2016-RVC VC (documentation/declaration) was 99.1% (95%CI: 98.2-99.6) in the semi-urban and 98.8% (95%CI: 96.5-99.6) in the rural areas. CONCLUSIONS: Although our VE estimates could be underestimated due to misclassification of measles status, the VC and VE point estimates of the 2016-SIA in the semi-urban area appear suboptimal, and in combination, could not limit the epidemic. Further research is needed on vaccination strategies adapted to urban contexts.
  • Prioritising pathogens for the management of severe febrile patients to improve clinical care in low- and middle-income countries

    Osborn, J; Roberts, T; Guillen, E; Bernal, O; Roddy, P; Ongarello, S; Sprecher, A; Page, AL; Ribeiro, I; Piriou, E; et al. (BioMed Central, 2020-02-10)
    BACKGROUND: Severe febrile illness without a known source (SFWS) is a challenge for clinicians when deciding how to manage a patient, particularly given the wide spectrum of potential aetiologies that contribute to fever. These infections are difficult to distinguish clinically, and accurate diagnosis requires a plethora of diagnostics including blood cultures, imaging techniques, molecular or serological tests, and more. When laboratory services are available, a limited test menu hinders clinical decision-making and antimicrobial stewardship, leading to empiric treatment and suboptimal patient outcomes. To specifically address SFWS, this work aimed to identify priority pathogens for a globally applicable panel for fever causing pathogens. METHOD: A pragmatic two-pronged approach combining currently available scientific data in an analytical hierarchy process and systematically gathered expert input, was designed to address the lack of comprehensive global aetiology data. The expert re-ranked list was then further adapted for a specific use case to focus on community acquired infections in whole blood specimens. The resulting list was further analysed to address different geographical regions (Asia, Africa, and Latin America), and Cohen kappa scores of agreement were calculated. RESULTS: The expert ranked prioritized pathogen list generated as part of this two-pronged approach included typhoidal Salmonella, Plasmodium species and Mycobacterium tuberculosis as the top 3 pathogens. This pathogen list was then further adapted for the SFWS use case to develop a final pathogen list to inform product development. Subsequent analysis comparing the relevance of the SFWS pathogen list to multiple populations and geographical regions showed that the SFWS prioritized list had considerable utility across Africa and Asia, but less so for Latin America. In addition, the list showed high levels of agreement across different patient sub-populations, but lower relevance for neonates and symptomatic HIV patients. CONCLUSION: This work highlighted once again the challenges of prioritising in global health, but it also shows that taking a two-pronged approach, combining available prevalence data with expert input, can result in a broadly applicable priority list. This comprehensive utility is particularly important in the context of product development, where a sufficient market size is essential to achieve a sustainable commercialized diagnostic product to address SFWS.
  • Knowledge, Awareness and Practices of Incident Cases of Dengue in Chandigarh

    Kaur, R; Rajvanshi, H (Advanced Research Publications, 2019-12-23)
    Introduction: Dengue is an endemic disease in India. Epidemics occur every year with incidence rising every year. Since 2010, Chandigarh has seen Dengue epidemics every year but the toll of reported confirmed cases has been very low. A study was undertaken to assess knowledge, awareness and practices among those who had already been diagnosed with dengue and followed up multiple times by Multipurpose Health Workers (MPHWs) at their homes. This study was conducted when both authors were post-graduate scholars at the Department of Public Health at Manipal Academy of Higher Education.Objective: To ascertain knowledge, awareness and practices regarding dengue among incident dengue cases of 2016 in Chandigarh. Methods: Retrospective Cohort study was conducted among the incident cases of dengue reported in 2016. The line list of cases was obtained from health department. Each household was visited once and face to face interviews were conducted with those willing to participate from January 2017 to March 2017. Using a modified WHO (World Health Organisation) questionnaire, 149 interviews were completed and analysed using descriptive analytical tools. Results: Data from the 149 interviews (57 males and 92 females) was used for primary analysis. Only 58.4% respondents were aware about dengue before diagnosis and 63.1% knew of its vector while only 10.1% were aware of the national programme and services available to them. Use of mosquito net was negligible (3.4%), even in rural areas. Screens on doors and windows were more common in urban area of Chandigarh. Conclusion: Since the study was conducted among incident cases, even after multiple visits conducted by MPHWs to the houses of these respondents, the knowledge regarding dengue was lower than expected.
  • 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.

View more