• Ebola haemorrhagic fever outbreak in Masindi District, Uganda: outbreak description and lessons learned

      Borchert, Matthias; Mutyaba, Imaam; Van Kerkhove, Maria D; Lutwama, Julius; Luwaga, Henry; Bisoborwa, Geoffrey; Turyagaruka, John; Pirard, Patricia; Ndayimirije, Nestor; Roddy, Paul; et al. (BioMed Central, 2011-12-28)
    • Ebola Management Centre Proximity Associated With Reduced Delays of Healthcare of Ebola Virus Disease (EVD) Patients, Tonkolili, Sierra Leone, 2014-15

      Theocharopoulos, G; Danis, K; Greig, J; Hoffmann, A; De Valk, H; Jimissa, A; Tejan, S; Sankoh, M; Kleijer, K; Turner, W; et al. (Public Library of Science, 2017-05-01)
      Between August-December 2014, Ebola Virus Disease (EVD) patients from Tonkolili District were referred for care to two Médecins Sans Frontières (MSF) Ebola Management Centres (EMCs) outside the district (distant EMCs). In December 2014, MSF opened an EMC in Tonkolili District (district EMC). We examined the effect of opening a district-based EMC on time to admission and number of suspect cases dead on arrival (DOA), and identified factors associated with fatality in EVD patients, residents in Tonkolili District. Residents of Tonkolili district who presented between 12 September 2014 and 23 February 2015 to the district EMC and the two distant EMCs were identified from EMC line-lists. EVD cases were confirmed by a positive Ebola PCR test. We calculated time to admission since the onset of symptoms, case-fatality and adjusted Risk Ratios (aRR) using Binomial regression. Of 249 confirmed Ebola cases, 206 (83%) were admitted to the distant EMCs and 43 (17%) to the district EMC. Of them 110 (45%) have died. Confirmed cases dead on arrival (n = 10) were observed only in the distant EMCs. The median time from symptom onset to admission was 6 days (IQR 4,8) in distant EMCs and 3 days (IQR 2,7) in the district EMC (p<0.001). Cases were 2.0 (95%CI 1.4-2.9) times more likely to have delayed admission (>3 days after symptom onset) in the distant compared with the district EMC, but were less likely (aRR = 0.8; 95%CI 0.6-1.0) to have a high viral load (cycle threshold ≤22). A fatal outcome was associated with a high viral load (aRR 2.6; 95%CI 1.8-3.6) and vomiting at first presentation (aRR 1.4; 95%CI 1.0-2.0). The opening of a district EMC was associated with earlier admission of cases to appropriate care facilities, an essential component of reducing EVD transmission. High viral load and vomiting at admission predicted fatality. Healthcare providers should consider the location of EMCs to ensure equitable access during Ebola outbreaks.
    • Ebola outbreak in Conakry, Guinea: Epidemiological, clinical, and outcome features

      Barry, M; Traoré, F A; Sako, F B; Kpamy, D O; Bah, E I; Poncin, M; Keita, S; Cisse, M; Touré, A (Elsevier, 2014-10-22)
      The authors studied the epidemiological, clinical, and outcome features of the Ebola virus disease in patients hospitalized at the Ebola treatment center (ETC) in Conakry to identify clinical factors associated with death.
    • Ebola outbreak in rural West Africa: epidemiology, clinical features and outcomes

      Dallatomasinas, Silvia; Crestani, Rosa; Squire, James Sylvester; Declerk, Hilde; Caleo, Grazia Marta; Wolz, Anja; Stinson, Kathyrn; Patten, Gabriela; Brechard, Raphael; Gbabai, Osman Bamba-Moi; et al. (Wiley-Blackwell, 2015-01-07)
      To describe Ebola cases in the district Ebola Management Centre of in Kailahun, a remote rural district of Sierra Leone, in terms of geographic origin, patient and hospitalization characteristics, treatment outcomes and time from symptom onset to admission.
    • Ebola Virus Disease Complications as Experienced by Survivors in Sierra Leone.

      Tiffany, Amanda; Vetter, Pauline; Mattia, John; Dayer, Julie-Anne; Bartsch, Maria; Kasztura, Miriam; Sterk, Esther; Tijerino, Ana Maria; Kaiser, Laurent; Ciglenecki, Iza (2016-03-21)
       Thousands of people have survived Ebola virus disease (EVD) during the ongoing outbreak. However, data about the frequency and risk factors of long-term post-EVD complications remain scarce. We describe the clinical characteristics of EVD survivors followed in a survivor clinic in Freetown, Sierra Leone.
    • Ebola Virus Disease in Pregnancy: Clinical, Histopathologic and Immunohistochemical Findings

      Muehlenbachs, A; de la Rosa Vázquez, O; Bausch, DG; Schafer, IJ; Paddock, CD; Nyakio, JP; Lame, P; Bergeron, E; McCollum, AM; Goldsmith, CS; et al. (Oxford University Press We regret that this article is behind a paywall., 2016-05-25)
      Here we describe clinicopathologic features of EVD in pregnancy. One woman infected with Sudan virus in Gulu, Uganda in 2000 had a stillbirth and survived, and another woman with Bundibugyo virus had a livebirth with maternal and infant death in Isiro, the Democratic Republic of the Congo in 2012. Ebolavirus antigen was seen in the syncytiotrophoblast and placental maternal mononuclear cells by immunohistochemistry, and no antigen was seen in fetal placental stromal cells or fetal organs. In the Gulu case, ebolavirus antigen localized to malaria pigment-laden macrophages. These data suggest trophoblast infection may be a mechanism of transplacental ebolavirus transmission.
    • Ebola Virus Disease in West Africa - Clinical Manifestations and Management

      Chertow, Daniel S; Kleine, Christian; Edwards, Jeffrey K; Scaini, Roberto; Giuliani, Ruggero; Sprecher, Armand (Massachusetts Medical Society, 2014-11-05)
      In resource-limited areas, isolation of the sick from the population at large has been the cornerstone of control of Ebola virus disease (EVD) since the virus was discovered in 1976.(1) Although this strategy by itself may be effective in controlling small outbreaks in remote settings, it has offered little hope to infected people and their families in the absence of medical care. In the current West African outbreak, infection control and clinical management efforts are necessarily being implemented on a larger scale than in any previous outbreak, and it is therefore appropriate to reassess traditional efforts at disease management. Having . . .
    • Ebola Virus Disease Outbreak in Isiro, Democratic Republic of the Congo, 2012: Signs and Symptoms, Management and Outcomes

      Kratz, Thomas; Roddy, Paul; Tshomba Oloma, Antoine; Jeffs, Benjamin; Pou Ciruelo, Diana; de la Rosa, Olimpia; Borchert, Matthias (Public Library of Science, 2015-06-24)
      Data collected during the 2012 Ebola virus disease (EVD) epidemic in the Democratic Republic of the Congo were analysed for clinical signs, symptoms and case fatality of EVD caused by Bundibugyo virus (BDBV), establishment of differential diagnoses, description of medical treatment and evaluation of the quality of clinical documentation. In a quantitative observational prospective study, global epidemiological data from 52 patients (34 patients within the community, 18 patients treated in the Ebola Treatment Centre) were entered anonymously into a database, subsequently matched and analysed. Relevant findings include an over-representation of females among community EVD cases (85.3%) and of community EVD cases in the age group of 15-54 years (82.4%). All ETC patients had fever (55.6% of all 18 ETC patients during their hospital stay) or self-reported fever (88.2% upon admission) at some point of time during their illness. Major symptoms of ETC patients during hospital stay included asthenia (82.4%), anorexia (82.4%), myalgia (70.6%), sore throat/difficulty swallowing (70.6%), arthralgia (76.5%) and nausea (70.6%). Gastrointestinal signs and symptoms (nausea, diarrhoea, vomiting) (76.4%) as well as general pain (94.1%) were frequent in ETC patients. The median duration of EVD was 18 days, while the mean incubation period was 11.3 days. Differential diagnosis of EVD included malaria (28.3%), intestinal parasitosis (10.9%), and infectious syndrome (10.9%). There was also an important variation in clinical evolvement. Quality of documentation was adversely affected by the way patient file contents were transferred from inside to outside the high-risk zone, entailing a mean mismatch value of 27.3% between patient file contents inside vs. outside the high-risk zone. This study adds further description of EVD (frequently non-specific signs and symptoms, non frequent bleeding, a long incubation period, long duration of disease) and emphasizes the need for improving clinical monitoring and documentation in EVD outbreak settings.
    • Ebola Virus Disease, Democratic Republic of the Congo, 2014

      Nanclares, C; Kapetshi, J; Lionetto, F; de la Rosa, O; Tamfun, JJ; Alia, M; Kobinger, G; Bernasconi, A (Center for Disease Control, 2016-09)
      During July-November 2014, the Democratic Republic of the Congo underwent its seventh Ebola virus disease (EVD) outbreak. The etiologic agent was Zaire Ebola virus; 66 cases were reported (overall case-fatality rate 74.2%). Through a retrospective observational study of confirmed EVD in 25 patients admitted to either of 2 Ebola treatment centers, we described clinical features and investigated correlates associated with death. Clinical features were mainly generic. At admission, 76% of patients had >1 gastrointestinal symptom and 28% >1 hemorrhagic symptom. The case-fatality rate in this group was 48% and was higher for female patients (67%). Cox regression analysis correlated death with initial low cycle threshold, indicating high viral load. Cycle threshold was a robust predictor of death, as were fever, hiccups, diarrhea, dyspnea, dehydration, disorientation, hematemesis, bloody feces during hospitalization, and anorexia in recent medical history. Differences from other outbreaks could suggest guidance for optimizing clinical management and disease control.
    • Ebola Virus Disease: An Update On Current Prevention and Management Strategies

      Trad, MA; Naughton, W; Yeung, A; Mazlin, L; O'sullivan, M; Gilroy, N; Fisher, DA; Stuart, RL (Elsevier, 2016-11-11)
      Ebola virus disease (EVD) is characterised by systemic viral replication, immuno-suppression, abnormal inflammatory responses, large volume fluid and electrolyte losses, and high mortality in under-resourced settings. There are various therapeutic strategies targeting EVD including vaccines utilizing different antigen delivery methods, antibody-based therapies and antiviral drugs. These therapies remain experimental, but received attention following their use particularly in cases treated outside West Africa during the 2014-15 outbreak, in which 20 (80%) out of 25 patients survived. Emerging data from current trials look promising and are undergoing further study, however optimised supportive care remains the key to reducing mortality from EVD.
    • Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone

      Park, Daniel J; Dudas, Gytis; Wohl, Shirlee; Goba, Augustine; Whitmer, Shannon L M; Andersen, Kristian G; Sealfon, Rachel S; Ladner, Jason T; Kugelman, Jeffrey R; Matranga, Christian B; et al. (2015-06-18)
      The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission.
    • The Ebola-effect in Guinea 2014-15: Tangled trends of malaria care in children under-five

      Kolie, D; Camara, BS; Delamou, A; Béavogui, AH; Hermans, V; Edwards, JK; Benedetti, G; Muller, CP; Griensven, JV; Zachariah, R (Public Library of Science, 2018-02-28)
      The 2014-15 Ebola outbreak in West Africa was disruptive for the general health services in the affected countries. This study assessed the impact of the outbreak on the reported number and management of malaria in children under-five in rural Guinea.
    • Ecological study of socio-economic indicators and prevalence of asthma in schoolchildren in urban Brazil.

      da Cunha, S S; Pujades-Rodriguez, M; Barreto, M L; Genser, B; Rodrigues, L C; Instituto de Saúde Coletiva, Universidade Federal de Bahia, Salvador, Brazil. cunhass@ufba.br (2007)
      BACKGROUND: There is evidence of higher prevalence of asthma in populations of lower socio-economic status in affluent societies, and the prevalence of asthma is also very high in some Latin American countries, where societies are characterized by a marked inequality in wealth. This study aimed to examine the relationship between estimates of asthma prevalence based on surveys conducted in children in Brazilian cities and health and socioeconomic indicators measured at the population level in the same cities. METHODS: We searched the literature in the medical databases and in the annals of scientific meeting, retrieving population-based surveys of asthma that were conducted in Brazil using the methodology defined by the International Study of Asthma and Allergies in Childhood. We performed separate analyses for the age groups 6-7 years and 13-14 years. We examined the association between asthma prevalence rates and eleven health and socio-economic indicators by visual inspection and using linear regression models weighed by the inverse of the variance of each survey. RESULTS: Six health and socioeconomic variables showed a clear pattern of association with asthma. The prevalence of asthma increased with poorer sanitation and with higher infant mortality at birth and at survey year, GINI index and external mortality. In contrast, asthma prevalence decreased with higher illiteracy rates. CONCLUSION: The prevalence of asthma in urban areas of Brazil, a middle income country, appears to be higher in cities with more marked poverty or inequality.
    • Effectiveness of Incidence Thresholds for Detection and Control of Meningococcal Meningitis Epidemics in Northern Togo.

      Kaninda, A V; Belanger, F; Lewis, R; Batchassi, E; Aplogan, A; Yakoua, Y; Paquet, C; Epicentre, 8 rue Saint-Sabin, 75011 Paris, France. (Published by Oxford University Press, 2000-10)
      BACKGROUND: Early outbreak detection is necessary for control of meningococcal meningitis epidemics. A weekly incidence of 15 cases per 100 000 inhabitants averaged over 2 consecutive weeks is recommended by the World Health Organization (WHO) for detection of meningitis epidemics in Africa. This and other thresholds are tested for ability to predict outbreaks and timeliness for control measures. METHODS: Meningitis cases recorded for 1990-1997 in health centres of northern Togo were reviewed. Weekly and annual incidences were determined for each district. Ability of different weekly incidence thresholds to detect outbreaks was assessed according to sensitivity, specificity, and positive and negative predictive values. The number of cases potentially prevented by reactive vaccination in 1997 was calculated for each threshold. RESULTS: Outbreaks occurred in 1995-1996 and in 1996-1997. The WHO-recommended threshold had good specificity but low sensitivity. Thresholds of 10 and 7 cases per 100,000 inhabitants in one week had sensitivity and specificity of 100% and increased the time available for intervention by more than one or two weeks, respectively. A maximum of 65% of cases could have been prevented during the 1997 epidemic, with up to 8% fewer cases prevented for each week of delay in achieving vaccine coverage. CONCLUSIONS: In northern Togo, thresholds of 7 or 10 cases per 100,000 inhabitants per week were excellent predictors of meningitis epidemics and allowed more time for a reactive vaccination strategy than current recommendations.
    • Effectiveness of One Dose of Oral Cholera Vaccine in Response to an Outbreak: A Case-Cohort Study

      Azman, AS; Parker, LA; Rumunu, J; Tadesse, F; Grandesso, F; Deng, LL; Lino, RL; Bior, BK; Lasuba, M; Page, AL; et al. (Elsevier, 2016-11-01)
      Oral cholera vaccines represent a new effective tool to fight cholera and are licensed as two-dose regimens with 2-4 weeks between doses. Evidence from previous studies suggests that a single dose of oral cholera vaccine might provide substantial direct protection against cholera. During a cholera outbreak in May, 2015, in Juba, South Sudan, the Ministry of Health, Médecins Sans Frontières, and partners engaged in the first field deployment of a single dose of oral cholera vaccine to enhance the outbreak response. We did a vaccine effectiveness study in conjunction with this large public health intervention.
    • 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.
    • Effects of Physical Therapy on Patients with Kashin-Beck Disease in Tibet.

      Mathieu, F; Suetens, C; Begaux, F; De Maertelaer, V; Hinsenkamp, M; Médecins Sant Frontières, Département Médical, Brussels, Belgium. francoise.mathieu@msf.be (Springer, 2001)
      A clinical trial of physical therapy treatment for patients suffering from Kashin-Beck disease (KBD) has been carried out in Tibet. One-hundred and thirty-five patients with Kashin-Beck disease were allocated to either physical therapy (72 patients) or prescription of multivitamins (63 patients). The patients were followed for 4 years. This study suggested a beneficial effect of physical treatment.
    • Efficacy and Effectiveness of an rVSV-Vectored Vaccine in Preventing Ebola Virus Disease: Final Results from the Guinea Ring Vaccination, Open-Label, Cluster-Randomised Trial (Ebola Ça Suffit!)

      Henao-Restrepo, AM; Camacho, A; Longini, IM; Watson, CH; Edmunds, WJ; Egger, M; Carroll, MW; Dean, NE; Diatta, I; Doumbia, M; et al. (Elsevier, 2016-12-23)
      rVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa.
    • Efficacy of artesunate-amodiaquine for treating uncomplicated falciparum malaria in sub-Saharan Africa: a multi-centre analysis.

      Zwang, Julien; Olliaro, Piero; Barennes, Hubert; Bonnet, Maryline; Brasseur, Philippe; Bukirwa, Hasifa; Cohuet, Sandra; D'Alessandro, Umberto; Djimdé, Abdulaye; Karema, Corine; et al. (2009-11)
      BACKGROUND: Artesunate and amodiaquine (AS&AQ) is at present the world's second most widely used artemisinin-based combination therapy (ACT). It was necessary to evaluate the efficacy of ACT, recently adopted by the World Health Organization (WHO) and deployed over 80 countries, in order to make an evidence-based drug policy. METHODS: An individual patient data (IPD) analysis was conducted on efficacy outcomes in 26 clinical studies in sub-Saharan Africa using the WHO protocol with similar primary and secondary endpoints. RESULTS: A total of 11,700 patients (75% under 5 years old), from 33 different sites in 16 countries were followed for 28 days. Loss to follow-up was 4.9% (575/11,700). AS&AQ was given to 5,897 patients. Of these, 82% (4,826/5,897) were included in randomized comparative trials with polymerase chain reaction (PCR) genotyping results and compared to 5,413 patients (half receiving an ACT). AS&AQ and other ACT comparators resulted in rapid clearance of fever and parasitaemia, superior to non-ACT. Using survival analysis on a modified intent-to-treat population, the Day 28 PCR-adjusted efficacy of AS&AQ was greater than 90% (the WHO cut-off) in 11/16 countries. In randomized comparative trials (n = 22), the crude efficacy of AS&AQ was 75.9% (95% CI 74.6-77.1) and the PCR-adjusted efficacy was 93.9% (95% CI 93.2-94.5). The risk (weighted by site) of failure PCR-adjusted of AS&AQ was significantly inferior to non-ACT, superior to dihydroartemisinin-piperaquine (DP, in one Ugandan site), and not different from AS+SP or AL (artemether-lumefantrine). The risk of gametocyte appearance and the carriage rate of AS&AQ was only greater in one Ugandan site compared to AL and DP, and lower compared to non-ACT (p = 0.001, for all comparisons). Anaemia recovery was not different than comparator groups, except in one site in Rwanda where the patients in the DP group had a slower recovery. CONCLUSION: AS&AQ compares well to other treatments and meets the WHO efficacy criteria for use against falciparum malaria in many, but not all, the sub-Saharan African countries where it was studied. Efficacy varies between and within countries. An IPD analysis can inform general and local treatment policies. Ongoing monitoring evaluation is required.
    • El Niño and the Shifting Geography of Cholera in Africa

      Moore, SM; Azman, AS; Zaitchik, BF; Mintz, ED; Brunkard, J; Legros, D; Hill, A; McKay, H; Luquero, FJ; Olson, D; et al. (Proceedings of the National Academy of Sciences of the United States, 2017-04-10)
      The El Niño Southern Oscillation (ENSO) and other climate patterns can have profound impacts on the occurrence of infectious diseases ranging from dengue to cholera. In Africa, El Niño conditions are associated with increased rainfall in East Africa and decreased rainfall in southern Africa, West Africa, and parts of the Sahel. Because of the key role of water supplies in cholera transmission, a relationship between El Niño events and cholera incidence is highly plausible, and previous research has shown a link between ENSO patterns and cholera in Bangladesh. However, there is little systematic evidence for this link in Africa. Using high-resolution mapping techniques, we find that the annual geographic distribution of cholera in Africa from 2000 to 2014 changes dramatically, with the burden shifting to continental East Africa-and away from Madagascar and portions of southern, Central, and West Africa-where almost 50,000 additional cases occur during El Niño years. Cholera incidence during El Niño years was higher in regions of East Africa with increased rainfall, but incidence was also higher in some areas with decreased rainfall, suggesting a complex relationship between rainfall and cholera incidence. Here, we show clear evidence for a shift in the distribution of cholera incidence throughout Africa in El Niño years, likely mediated by El Niño's impact on local climatic factors. Knowledge of this relationship between cholera and climate patterns coupled with ENSO forecasting could be used to notify countries in Africa when they are likely to see a major shift in their cholera risk.