• 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 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.
    • Clinical and Epidemiological Aspects of Diphtheria: A Systematic Review and Pooled Analysis.

      Truelover, SA; Keegan, LT; Moss, WJ; Chaisson, LH; Macher, E; Azman, AS; Lessler, J (Oxford University Press, 2020-06-24)
      Background Diphtheria, once a major cause of childhood morbidity and mortality, all but disappeared following introduction of diphtheria vaccine. Recent outbreaks highlight the risk diphtheria poses when civil unrest interrupts vaccination and healthcare access. Lack of interest over the last century resulted in knowledge gaps about diphtheria’s epidemiology, transmission, and control. Methods We conducted 9 distinct systematic reviews on PubMed and Scopus (March–May 2018). We pooled and analyzed extracted data to fill in these key knowledge gaps. Results We identified 6934 articles, reviewed 781 full texts, and included 266. From this, we estimate that the median incubation period is 1.4 days. On average, untreated cases are colonized for 18.5 days (95% credible interval [CrI], 17.7–19.4 days), and 95% clear Corynebacterium diphtheriae within 48 days (95% CrI, 46–51 days). Asymptomatic carriers cause 76% (95% confidence interval, 59%–87%) fewer cases over the course of infection than symptomatic cases. The basic reproductive number is 1.7–4.3. Receipt of 3 doses of diphtheria toxoid vaccine is 87% (95% CrI, 68%–97%) effective against symptomatic disease and reduces transmission by 60% (95% CrI, 51%–68%). Vaccinated individuals can become colonized and transmit; consequently, vaccination alone can only interrupt transmission in 28% of outbreak settings, making isolation and antibiotics essential. While antibiotics reduce the duration of infection, they must be paired with diphtheria antitoxin to limit morbidity. Conclusions Appropriate tools to confront diphtheria exist; however, accurate understanding of the unique characteristics is crucial and lifesaving treatments must be made widely available. This comprehensive update provides clinical and public health guidance for diphtheria-specific preparedness and response.
    • Clinical Chemistry of Patients With Ebola in Monrovia, Liberia

      de Wit, E; Kramer, S; Prescott, J; Rosenke, K; Falzarano, D; Marzi, A; Fischer, RJ; Safronetz, D; Hoenen, T; Groseth, A; et al. (Oxford University Press, 2016-07-28)
      The development of point-of-care clinical chemistry analyzers has enabled the implementation of these ancillary tests in field laboratories in resource-limited outbreak areas. The Eternal Love Winning Africa (ELWA) outbreak diagnostic laboratory, established in Monrovia, Liberia, to provide Ebola virus and Plasmodium spp. diagnostics during the Ebola epidemic, implemented clinical chemistry analyzers in December 2014. Clinical chemistry testing was performed for 68 patients in triage, including 12 patients infected with Ebola virus and 18 infected with Plasmodium spp. The main distinguishing feature in clinical chemistry of Ebola virus-infected patients was the elevation in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyltransferase levels and the decrease in calcium. The implementation of clinical chemistry is probably most helpful when the medical supportive care implemented at the Ebola treatment unit allows for correction of biochemistry derangements and on-site clinical chemistry analyzers can be used to monitor electrolyte balance.
    • Clinical predictor of mortality in patients with Ebola virus disease

      Barry, Moumié; Touré, Abdoulaye; Traoré, Fodé Amara; Sako, Fodé-Bangaly; Sylla, D; Kpamy, Dimai Ouo; Bah, Elhadj Ibrahima; Bangoura, M'Mah; Poncin, Marc; Keita, Sakoba; et al. (Oxford University Press, 2015-03-13)
      In an observational cohort study including 89 Ebola patients, predictor factors of death were analyzed. The crude mortality rate was 43.8%. Myalgia (OR; 4.04; P=0.02), hemorrhage (OR=3.52; P=0.02), and difficulty breathing (OR= 5.75; P=0.01) were independently associated with death.
    • Concomitant treatment of chronic hepatitis C with direct acting antivirals and multidrug-resistant tuberculosis is effective and safe

      Melikyan, N; Huerga, H; Atshemyan, H; Kirakosyan, O; Sargsyants, N; Aydinyan, T; Saribekyan, N; Khachatryan, N; Oganezova, I; Falcao, J; et al.
      We assessed effectiveness and safety of concomitant chronic hepatitis C (HCV) treatment with direct acting antivirals (DAAs) and multidrug-resistant tuberculosis (MDR-TB). Of 322 MDR-TB patients (19.4% HCV), 30 were treated concomitantly (23.3% HIV-positive). Overall, 76.7% achieved HCV treatment success (95.8% among tested). One patient (3.3%) experienced a serious adverse event.
    • Constraints in the diagnosis and treatment of Lassa Fever and the effect on mortality in hospitalized children and women with obstetric conditions in a rural district hospital in Sierra Leone

      Dahmane, A; van Griensven, J; Van Herp, M; Van den Bergh, R; Nzomukunda, Y; Prior, J; Alders, P; Jambai, A; Zachariah, R (Oxford University Press, 2014-03)
      Lassa fever (LF) is an acute viral haemorrhagic infection, endemic in West Africa. Confirmatory diagnosis and treatment (ribavirin) is difficult, expensive, and restricted to specialised hospitals. Among confirmed and suspected LF cases, we report on clinical and laboratory features, timing and administration of ribavirin and the relationship with case fatality.
    • The contribution of Ebola viral load at admission and other patient characteristics to mortality in a Médecins Sans Frontières (MSF) Ebola Case Management Centre (CMC), Kailahun, Sierra Leone, June -October, 2014

      Fitzpatrick, Gabriel; Vogt, Florian; Gbabai, Osman B Moi; Decroo, Tom; Keane, Marian; De Clerck, Hilde; Grolla, Allen; Brechard, Raphael; Stinson, Kathryn; Van Herp, Michel (Oxford University Press, 2015-05-22)
      This paper describes patient characteristics, including Ebola viral load, associated with mortality in an MSF Ebola case management centre. Out of 780 admissions between June and October 2014, 525 (67%) were positive for Ebola with a known outcome. The crude mortality rate was 51% (270/525). Ebola viral load (whole blood sample) data was available on 76% (397/525) of patients. Univariate analysis indicated viral load at admission, age, symptom duration prior to admission and distance travelled to the CMC were associated with mortality (p value<0.05). The multivariable model predicted mortality in those with a viral load at admission greater than 10 million copies per millilitre (p value<0.05, Odds Ratio>10), aged 50 years or more (p value=0.08, Odds Ratio=2) and symptom duration prior to admission less than 5 days (p value=0.14). The presence of confusion, diarrhoea and conjunctivitis were significantly higher (p value<0.05) in Ebola patients who died. These findings highlight the importance viral load at admission has on mortality outcomes and could be used to cohort cases with viral loads greater than 10 million copies into dedicated wards with more intensive medical support to further reduce mortality.
    • Evaluation of Pastorex Meningitis Kit Performance for the Rapid Identification of Neisseria Meningitidis Serogroup C in Nigeria

      Uadiale, K; Bestman, A; Kamau, C; Caugant, DA; Greig, J (Oxford University Press, 2016-07)
      Neisseria meningitidis serogroup C (NmC) has caused outbreaks in Nigeria of increasing size in three consecutive years since 2013. Rapid diagnostic tests (RDTs) for meningitis can facilitate quick identification of the causative pathogen; Pastorex can detect N. meningitidis serogroups A, C (NmC), Y/W135, N. meningitidis serogroup B/Escherichia coli K1, Haemophilus influenzae type b (Hib), Streptococcus pneumoniae, and group B Streptococcus. There is no published field evaluation of Pastorex in the identification of NmC. We report our experience with Pastorex in detecting NmC in field conditions.
    • Field evaluation of capillary blood samples as a collection specimen for the rapid diagnosis of Ebola virus infection during an outbreak emergency

      Strecker, Thomas; Palyi, Bernadett; Ellerbrok, Heinz; Jonckheere, Sylvie; de Clerck, Hilde; Bore, Joseph Akoi; Gabriel, Martin; Stoecker, Kilian; Eickmann, Markus; van Herp, Michel; et al. (Oxford University Press, 2015-05-19)
      Reliable reverse-transcriptase polymerase chain reaction (RT-PCR)-based diagnosis of Ebola virus infection currently requires a blood sample obtained by intravenous puncture. During the current Ebola outbreak in Guinea, we evaluated the usability of capillary blood samples collected from fingersticks of patients suspected of having Ebola virus disease (EVD) for field diagnostics during an outbreak emergency.
    • From Risk to Care: The Hepatitis C Screening and Diagnostic Cascade in a Primary Health Care Clinic in Karachi, Pakistan—a Cohort Study

      Khalid, GG; Kyaw, KWY; Bousquet, C; Auat, R; Donchuk, D; Trickey, A; Hamid, S; Qureshi, H; Mazzeo, V; Aslam, K; et al. (Oxford University Press, 2018-12-28)
      Background In the high-prevalence setting of Pakistan, screening, diagnosis and treatment services for chronic hepatitis C (CHC) patients are commonly offered in specialized facilities. We aimed to describe the cascade of care in a Médecins Sans Frontières primary health care clinic offering CHC care in an informal settlement in Karachi, Pakistan. Methods This was a retrospective cohort analysis using routinely collected data. Three different screening algorithms were assessed among patients with one or more CHC risk factors. Results Among the 87 348 patients attending the outpatient clinic, 5003 (6%) presented with one or more risk factors. Rapid diagnostic test (RDT) positivity was 38% overall. Approximately 60% of the CHC patients across all risk categories were in the early stage of the disease, with an aspartate aminotransferase:platelet ratio index score <1. The sequential delays in the cascade differed between the three groups, with the interval between screening and treatment initiation being the shortest in the cohort tested with GeneXpert onsite. Conclusions Delays between screening and treatment can be reduced by putting in place more patient-centric testing algorithms. New strategies, to better identify and treat the hidden at-risk populations, should be developed and implemented.
    • 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'.
    • hlers

      Mashe, T; Leekitcharoenphon, P; Mtapuri-Zinyowera, S; Kingsley, RA; Robertson, V; Tarupiwa, A; Kock, MM; Makombe, EP; Chaibva, BV; Manangazira, P; et al. (Oxford University Press, 2020-12-21)
      Background Typhoid fever, caused by S. enterica ser. Typhi, continues to be a substantial health burden in developing countries. Little is known of the genotypic diversity of S. enterica ser. Typhi in Zimbabwe, but this is key for understanding the emergence and spread of this pathogen and devising interventions for its control. Objectives To report the molecular epidemiology of S. enterica ser. Typhi outbreak strains circulating from 2012 to 2019 in Zimbabwe, using comparative genomics. Methods : A review of typhoid cases records from 2012 to 2019 in Zimbabwe was performed. The phylogenetic relationship of outbreak isolates from 2012 to 2019 and emergence of antibiotic resistance was investigated by whole-genome sequence analysis. Results A total 22 479 suspected typhoid cases, 760 confirmed cases were reported from 2012 to 2019 and 29 isolates were sequenced. The majority of the sequenced isolates were predicted to confer resistance to aminoglycosides, β-lactams, phenicols, sulphonamides, tetracycline and fluoroquinolones (including qnrS detection). The qnrS1 gene was associated with an IncN (subtype PST3) plasmid in 79% of the isolates. Whole-genome SNP analysis, SNP-based haplotyping and resistance determinant analysis showed that 93% of the isolates belonged to a single clade represented by multidrug-resistant H58 lineage I (4.3.1.1), with a maximum pair-wise distance of 22 SNPs. Conclusions This study has provided detailed genotypic characterization of the outbreak strain, identified as S. Typhi 4.3.1.1 (H58). The strain has reduced susceptibility to ciprofloxacin due to qnrS carried by an IncN (subtype PST3) plasmid resulting from ongoing evolution to full resistance.
    • '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.
    • Increased risk of acquisition and transmission of ESBL-producing Enterobacteriaceae in malnourished children exposed to amoxicillin

      Maataoui1, M; Et al (Oxford University Press, 2019)
      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, placebocontrolled 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.
    • Interpretation of Negative Molecular Test Results in Patients with Suspected or Confirmed Ebola Virus Disease: Report of Two Cases

      Edwards, Jeffrey K.; Kleine, Christian; Munster, Vincent; Giuliani, Ruggero; Massaquoi, Moses; Sprecher, Armand; Chertow, Daniel S. (Oxford University Press, 2015-09-19)
    • Measles outbreaks in the Mozambican refugee camps in Malawi: the continued need for an effective vaccine.

      Porter, J D; Gastellu-Etchegorry, M; Navarre, I; Lungu, G; Moren, A; Epicentre, Paris, France. (Oxford University Press, 1990-12)
      Between November 1988 and January 1989, measles outbreaks occurred in 11 Mozambican refugee camps in Malawi with five camps principally affected. A total of 1214 cases were reported. Despite the reduction of the age of measles vaccination to six months in 1987, attack rates were highest in children aged 6-9 months (10-26%); rates were also high in the 0-5 month age group (3-21%). The case-fatality rate was high among children less than five years old (15-21%). Children were being inappropriately vaccinated, either being vaccinated at less than six months of age (2-29%) or failing to receive a second dose if vaccinated at six months (0-25%). With vaccine coverage between 66-87%, vaccine efficacy in children less than five years old was estimated to be more than 90% in the camps principally affected. Reduction of the age of vaccination leads to logistical problems in vaccine delivery in refugee situations. These outbreaks again indicate the need to improve vaccine coverage with the existing Schwarz vaccine, and also highlight the urgent need for an effective single dose measles vaccine for children less than nine months of age.
    • Micro-hotspots of Risk in Urban Cholera Epidemics

      Azman, AS; Luquero, FJ; Salje, H; Naibei Mbaïbardoum, N; Adalbert, N; Ali, M; Bertuzzo, E; Finger, F; Toure, B; Massing, LA; et al. (Oxford University Press, 2018-05-11)
      Targeted interventions have been delivered to neighbors of cholera cases in major epidemic responses globally despite limited evidence for the impact of such targeting. Using data from urban epidemics in Chad and D.R. Congo we estimate the extent of spatiotemporal zones of increased cholera risk around cases. In both cities, we found zones of increased risk of at least 200-meters during the 5-days immediately following case presentation to a clinic. Risk was highest for those living closest to cases and diminished in time and space similarly across settings. These results provide a rational basis for rapidly delivering targeting interventions.
    • More Challenges From Ebola: Infection of the Central Nervous System

      Wong, G; Qiu, X; Bi, Y; Formenty, P; Sprecher, A; Jacobs, M; Gao, GF; Kobinger, G (Oxford University Press, 2016-10-05)
    • A Multisectoral Emergency Response Approach to a Cholera Outbreak in Zambia: October 2017-February 2018

      Kapata, N; Sinyange, N; Mazaba, ML; Musonda, K; Hamoonga, R; Kapina, M; Zyambo, K; Malambo, W; Yard, E; Riggs, M; et al. (Oxford University Press, 2018-09-11)