• Brain injury: Iraq's unseen burden of wounded civilians

      Guerrier, Gilles; Baron, Emmanuel; Fakri, Rasheed; Mouniaman, Isabelle; Epicentre, Paris, France; Médecins Sans Frontières, Amman, Jordan; Médecins Sans Frontières, Paris, France (Nature Publishing Group, 2011-10-27)
      The burden of war-related mental disorders is well documented among US veterans (Nature 477, 390–393; 2011), but not among civilians in Iraq. This oversight must be rectified so that adequate medical support can be provided to the Iraqi people. US combat troops will soon depart Iraq, leaving Iraqis to cope with the consequences of the 2003 invasion. Although the number of violent deaths is falling, civilians have been killed almost every day this year, most of them in coordinated bomb attacks. Roadside blasts cause long-term disabilities and societal effects among injured civilians. However, these have been largely neglected by the media and no systematic surveillance has been undertaken.
    • Genomic Insights into the 2016-2017 Cholera Epidemic in Yemen

      Weill, FX; Domman, D; Njamkepo, E; Almesbahi, AA; Naji, M; Nasher, SS; Rakesh, A; Assiri, AM; Sharma, NC; Kariuki, S; et al. (Nature Publishing Group, 2019-01-02)
      Yemen is currently experiencing, to our knowledge, the largest cholera epidemic in recent history. The first cases were declared in September 2016, and over 1.1 million cases and 2,300 deaths have since been reported1. Here we investigate the phylogenetic relationships, pathogenesis and determinants of antimicrobial resistance by sequencing the genomes of Vibrio cholerae isolates from the epidemic in Yemen and recent isolates from neighbouring regions. These 116 genomic sequences were placed within the phylogenetic context of a global collection of 1,087 isolates of the seventh pandemic V. cholerae serogroups O1 and O139 biotype El Tor2-4. We show that the isolates from Yemen that were collected during the two epidemiological waves of the epidemic1-the first between 28 September 2016 and 23 April 2017 (25,839 suspected cases) and the second beginning on 24 April 2017 (more than 1 million suspected cases)-are V. cholerae serotype Ogawa isolates from a single sublineage of the seventh pandemic V. cholerae O1 El Tor (7PET) lineage. Using genomic approaches, we link the epidemic in Yemen to global radiations of pandemic V. cholerae and show that this sublineage originated from South Asia and that it caused outbreaks in East Africa before appearing in Yemen. Furthermore, we show that the isolates from Yemen are susceptible to several antibiotics that are commonly used to treat cholera and to polymyxin B, resistance to which is used as a marker of the El Tor biotype.
    • Global Phylogeography and Evolutionary History of Shigella Dysenteriae Type 1

      Njamkepo, E; Fawal, N; Tran-Dien, A; Hawkey, J; Strockbine, N; Jenkins, C; Talukder, KA; Bercion, R; Kuleshov, K; Kolínská, R; et al. (Nature Publishing Group, 2016-03-21)
      Together with plague, smallpox and typhus, epidemics of dysentery have been a major scourge of human populations for centuries(1). A previous genomic study concluded that Shigella dysenteriae type 1 (Sd1), the epidemic dysentery bacillus, emerged and spread worldwide after the First World War, with no clear pattern of transmission(2). This is not consistent with the massive cyclic dysentery epidemics reported in Europe during the eighteenth and nineteenth centuries(1,3,4) and the first isolation of Sd1 in Japan in 1897(5). Here, we report a whole-genome analysis of 331 Sd1 isolates from around the world, collected between 1915 and 2011, providing us with unprecedented insight into the historical spread of this pathogen. We show here that Sd1 has existed since at least the eighteenth century and that it swept the globe at the end of the nineteenth century, diversifying into distinct lineages associated with the First World War, Second World War and various conflicts or natural disasters across Africa, Asia and Central America. We also provide a unique historical perspective on the evolution of antibiotic resistance over a 100-year period, beginning decades before the antibiotic era, and identify a prevalent multiple antibiotic-resistant lineage in South Asia that was transmitted in several waves to Africa, where it caused severe outbreaks of disease.
    • Immune Responses to an Oral Cholera Vaccine in Internally Displaced Persons in South Sudan

      Iyer, AS; Bouhenia, M; Rumunu, J; Abubakar, A; Gruninger, RJ; Pita, J; Lino, RL; Deng, LL; Wamala, JF; Ryan, ET; et al. (Nature Publishing Group, 2016-10-24)
      Despite recent large-scale cholera outbreaks, little is known about the immunogenicity of oral cholera vaccines (OCV) in African populations, particularly among those at highest cholera risk. During a 2015 preemptive OCV campaign among internally displaced persons in South Sudan, a year after a large cholera outbreak, we enrolled 37 young children (1-5 years old), 67 older children (6-17 years old) and 101 adults (≥18 years old), who received two doses of OCV (Shanchol) spaced approximately 3 weeks apart. Cholera-specific antibody responses were determined at days 0, 21 and 35 post-immunization. High baseline vibriocidal titers (>80) were observed in 21% of the participants, suggesting recent cholera exposure or vaccination. Among those with titers ≤80, 90% young children, 73% older children and 72% adults seroconverted (≥4 fold titer rise) after the 1(st) OCV dose; with no additional seroconversion after the 2(nd) dose. Post-vaccination immunological endpoints did not differ across age groups. Our results indicate Shanchol was immunogenic in this vulnerable population and that a single dose alone may be sufficient to achieve similar short-term immunological responses to the currently licensed two-dose regimen. While we found no evidence of differential response by age, further immunologic and epidemiologic studies are needed.
    • 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.
    • Unique Human Immune Signature of Ebola Virus Disease in Guinea

      Ruibal, P; Oestereich, L; Lüdtke, A; Becker-Ziaja, B; Wozniak, DM; Kerber, R; Korva, M; Cabeza-Cabrerizo, M; Bore, JA; Koundouno, FR; et al. (Nature Publishing Group, 2016-05-05)
      Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD. In particular, very little is known about human immune responses to Ebola virus. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4(+) and CD8(+) T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.