Vinh-Kim Nguyen

Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea

Background Ebola virus disease (EVD) is a highly lethal condition for which no specific treatment has proven efficacy. In September 2014, while the Ebola outbreak was at its peak, the World Health Organization released a short list of drugs suitable for EVD research. Favipiravir, an antiviral developed for the treatment of severe influenza, was one of these. In late 2014, the conditions for starting a randomized Ebola trial were not fulfilled for two reasons. One was the perception that, given the high number of patients presenting simultaneously and the very high mortality rate of the disease, it was ethically unacceptable to allocate patients from within the same family or village to receive or not receive an experimental drug, using a randomization process impossible to understand by very sick patients. The other was that, in the context of rumors and distrust of Ebola treatment centers, using a randomized design at the outset might lead even more patients to refuse to seek care. Therefore, we chose to conduct a multicenter non-randomized trial, in which all patients would receive favipiravir along with standardized care. The objectives of the trial were to test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak, and to collect data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with EVD. The trial was not aimed at directly informing future guidelines on Ebola treatment but at quickly gathering standardized preliminary data to optimize the design of future studies. Methods and Findings Inclusion criteria were positive Ebola virus reverse transcription PCR (RT-PCR) test, age ≥ 1 y, weight ≥ 10 kg, ability to take oral drugs, and informed consent. All participants received oral favipiravir (day 0: 6,000 mg; day 1 to day 9: 2,400 mg/d). Semi-quantitative Ebola virus RT-PCR (results expressed in “cycle threshold” [Ct]) and biochemistry tests were performed at day 0, day 2, day 4, end of symptoms, day 14, and day 30. Frozen samples were shipped to a reference biosafety level 4 laboratory for RNA viral load measurement using a quantitative reference technique (genome copies/milliliter). Outcomes were mortality, viral load evolution, and adverse events. The analysis was stratified by age and Ct value. A “target value” of mortality was defined a priori for each stratum, to guide the interpretation of interim and final analysis. Between 17 December 2014 and 8 April 2015, 126 patients were included, of whom 111 were analyzed (adults and adolescents, ≥13 y, n = 99; young children, ≤6 y, n = 12). Here we present the results obtained in the 99 adults and adolescents. Of these, 55 had a baseline Ct value ≥ 20 (Group A Ct ≥ 20), and 44 had a baseline Ct value < 20 (Group A Ct < 20). Ct values and RNA viral loads were well correlated, with Ct = 20 corresponding to RNA viral load = 7.7 log10 genome copies/ml. Mortality was 20% (95% CI 11.6%–32.4%) in Group A Ct ≥ 20 and 91% (95% CI 78.8%–91.1%) in Group A Ct < 20. Both mortality 95% CIs included the predefined target value (30% and 85%, respectively). Baseline serum creatinine was ≥110 μmol/l in 48% of patients in Group A Ct ≥ 20 (≥300 μmol/l in 14%) and in 90% of patients in Group A Ct < 20 (≥300 μmol/l in 44%). In Group A Ct ≥ 20, 17% of patients with baseline creatinine ≥110 μmol/l died, versus 97% in Group A Ct < 20. In patients who survived, the mean decrease in viral load was 0.33 log10 copies/ml per day of follow-up. RNA viral load values and mortality were not significantly different between adults starting favipiravir within <72 h of symptoms compared to others. Favipiravir was well tolerated. Conclusions In the context of an outbreak at its peak, with crowded care centers, randomizing patients to receive either standard care or standard care plus an experimental drug was not felt to be appropriate. We did a non-randomized trial. This trial reaches nuanced conclusions. On the one hand, we do not conclude on the efficacy of the drug, and our conclusions on tolerance, although encouraging, are not as firm as they could have been if we had used randomization. On the other hand, we learned about how to quickly set up and run an Ebola trial, in close relationship with the community and non-governmental organizations; we integrated research into care so that it improved care; and we generated knowledge on EVD that is useful to further research. Our data illustrate the frequency of renal dysfunction and the powerful prognostic value of low Ct values. They suggest that drug trials in EVD should systematically stratify analyses by baseline Ct value, as a surrogate of viral load. They also suggest that favipiravir monotherapy merits further study in patients with medium to high viremia, but not in those with very high viremia. Trial registration ClinicalTrials.gov NCT02329054

Changing therapeutic geographies of the Iraqi and Syrian wars

The health consequences of the ongoing US-led war on terror and civil armed conflicts in the Arab world are much more than the collateral damage inflicted on civilians, infrastructure, environment, and health systems. Protracted war and armed conflicts have displaced populations and led to lasting transformations in health and health care. In this report, we analyse the effects of conflicts in Iraq and Syria to show how wars and conflicts have resulted in both the militarisation and regionalisation of health care, conditions that complicate the rebuilding of previously robust national health-care systems. Moreover, we show how historical and transnational frameworks can be used to show the long-term consequences of war and conflict on health and health care. We introduce the concept of therapeutic geographies--defined as the geographic reorganisation of health care within and across borders under conditions of war.

Biological Validation of Self-Reported Condom Use Among Sex Workers in Guinea.

Self-reported condom use may be prone to social desirability bias. Our aim was to assess the validity of self-reported condom use in a population of female sex workers using prostate specific antigen (PSA) as a gold standard biomarker of recent unprotected vaginal intercourse. We collected data on 223 sex-workers in Conakry, Guinea in order to assess the sensitivity and specificity of self-reported condom use as well as to examine the predictors of discordance between self-report and PSA presence. PSA was detected in 38.4% of samples. Sensitivity of self-reported condom use was 14.6% and its specificity was 94.7%. Self-perceived high risk of HIV infection was the only significant independent predictor of misreported condom use. PSA could be useful to validate self-reported condom use in surveys and to allow a better understanding of factors associated with social desirability in sexual behaviour reporting.

Science, technology, power and sex: PrEP and HIV-positive gay men in Paris

Abstract The pre-exposure prophylaxis (PrEP) drug Truvada is a new HIV prevention technology that is predominantly promoted as relevant to HIV-negative gay men. This paper explores what PrEP represents for HIV-positive gay men living in Paris, based upon data collected through interviews and ethnographic research. While HIV-positive gay men do not directly consume Truvada through PrEP, they nonetheless hold opinions and understandings of this drug, specifically as it relates to their own sexuality. This paper expands the representations and meanings of this new technology in a different light through the voices of gay men living with HIV in Paris. The main argument of this article is that PrEP as an additional HIV prevention tool blurs the lines between science, technologies and human sexuality.

Nutritional status of HIV-infected patients during the first year HAART in two West African cohorts

ObjectiveTo examine the association between nutritional markers at initiation and during follow up in two different cohorts of HIV-infected adults initiating highly active antiretroviral therapy (HAART) in West Africa.MethodsThe ATARAO study was a one year prospective study carried in Mali. It consisted of a sample of consecutive patients initiating HAART in one of four participating centers during that period. Data were collected at time of treatment initiation (baseline) and every 3xa0months thereafter. The ANRS 1290 study followed Senegalese patients recruited in similar conditions. Bivariate analyses were used to identify nutritional and immunological covariates of malnutrition at baseline. Longitudinal trajectories of body mass index, hemoglobin and albumin, and their associated factors, were evaluated using mixed linear models.ResultsIn ATARAO, 250 participants were retained for analyses; of which, 36% had a BMIu2009<u200918.5xa0kg/m2, nearly 60% were anemic and 47.4% hypoalbuminemic at time of treatment initiation. At baseline, low hemoglobin, hypoalbuminemia and low CD4 levels were associated with a BMIu2009<u200918.5xa0kg/m2. Similarly, low BMI, low albumin and low CD4 counts were linked to anemia; while, hypoalbuminemia was associated with low hemoglobin levels and CD4 counts. In ANRS, out of the 372 participants retained for analyses, 31% had a low BMI and almost 70% were anemic. At baseline, low BMI was associated with low hemoglobin levels and CD4 counts, while anemia was associated with low CD4 counts and female sex. While treatment contributed to early gains in BMI, hemoglobin and albumin in the first 6xa0months of treatment, initial improvements plateaued or subsided thereafter. Despite HAART, malnutrition persisted in both cohorts after one year, especially in those who were anemic, hypoalbuminemic or had a low BMI at baseline.ConclusionIn ATARAO and ANRS, malnutrition was common across all indicators (BMI, hemoglobin, albumin) and persisted despite treatment. Low BMI, anemia and hypoalbuminemia were associated with attrition, and with a deficient nutritional and immunological status at baseline, as well as during treatment. In spite of therapy, malnutrition is associated with negative clinical and treatment outcomes which suggests that HAART may not be sufficient to address co-existing nutritional deficiencies.

Evaluability Assessment of an immunization improvement strategy in rural Burkina Faso: Intervention theory versus reality, information need and evaluations

An innovative immunization improvement strategy was proposed by the CRSN (Centre de Recherche en Santé de Nouna) to improve the low coverage rate for children aged 0-11 months in the health district of Nouna in Burkina Faso. This article reports on the Evaluability Assessment (EA) study that aimed to orient decisions for its evaluation in close relationship with the information needs of the stakeholders. Various methods were used, including document reviews, individual interviews, focus group discussions, meetings, literature reviews and site visits. A description of the intervention theory and philosophy is provided with its logic models and its reality documented. Lessons on the procedure include the importance of the position of the evaluability assessor, the value of replicating some steps of the assessment and the relationships between EA and process evaluation. The evaluability study concludes that the intervention had some evaluable components. To satisfy the stakeholders needs, the initially planned community randomized controlled trial can be maintained and complemented with a process evaluation. There is a need to provide sufficient information on the cost of the intervention. This will inform decision makers on the possibility of replicating the intervention in other contexts.

Vaccination and blood sampling acceptability during Ramadan fasting month: A cross-sectional study in Conakry, Guinea

INTRODUCTIONnThere are few data on the acceptability of vaccination or blood sampling during Ramadan fasting month in Muslim countries. This could impact vaccination campaigns, clinical trials or healthcare during Ramadan.nnnMETHODSnUsing a semi-structured questionnaire, we conducted a cross-sectional study on 201 practising Muslims and 10 religious leaders in Conakry, Guinea in the wake of the recent epidemic Ebola epidemic. Acceptability of vaccination and blood sampling during Ramadan were investigated as well as reasons for refusal.nnnRESULTSnVaccination was judged acceptable during Ramadan by 46% (93/201, 95% CI 0.40-0.53) of practising Muslims versus 80% (8/10, 95% CI 0.49-0.94) of religious leaders (p=0.11). Blood sampling was judged acceptable during Ramadan by 54% (108/201, 95% CI 0.47-0.60) of practising Muslims versus 80% (8/10, 95% CI 0.49-0.94) of religious leaders (p=0.19). The percentage of participants that judged both blood sampling and vaccination acceptable during Ramadan was 40% (81/201, 95% CI 0.34-0.47) for practising Muslims versus 80% (8/10, 95% CI 0.49-0.94) for religious leaders (p=0.048). The most common reasons for refusal of vaccination or blood sampling were that nothing should enter or leave the body during Ramadan (43%), that adverse events could lead to breaking the fast (32%), that blood should not be seen during Ramadan (9%) and that the Quran explicitly forbids it (9%).nnnDISCUSSIONnAlthough most Muslims leaders and scientists consider that injections including immunization and blood sampling should be authorized during Ramadan, many Muslims in our study judged vaccination or blood sampling unacceptable when fasting. Widely available recommendations on healthcare during Ramadan would be useful to inform Muslims.

Commentary on failure in HIV research

The Zollverein complex, in the Ruhr Valley, comprises what was at one point the largest coalmine in Germany. The mine is now long closed and was left abandoned for 15 years until, in 2001, it was declared a UNESCOWorld Heritage site and turned into a museum. On a sprawling site, massive buildings many built in the Bauhaus style of the 1930s stand eerily empty, as the Museum and a smattering of cultural and tech industries occupy only a fraction of the complex. In the Museum itself, one can admire the inanimate carcasses of the massive machines and structures that were used to process the coal. Alongside are photographs of the working class communities and way of life that emerged in the Ruhr Valley from the mid-nineteenth century with the industrialization that the mines made possible. An aura of failure hangs over the site the rusting machinery, the decaying buildings signal failure to adapt, failure to transform. Yet the sense of failure is belied by the burgeoning tech industries that have taken root on the site, and by the massive rave parties to which Europe’s post-industrial youth flock, and for which the site is an ideal setting. If the Zollverein complex can function as a synecdoche for the broad structural transformations of an epoch, the first exhibits in theMuseum of Failed HIV Research proposed here point to a broader history, that of what Cindy Patton first called the AIDS Industry and the transformations in the international health apparatus it heralded. When Patton coined the term, it was 1989, the year the Berlin wall crumbled: before antiretrovirals, before mass access to the web, before Global Health. Just as coal begat the industrial revolution, AIDS was the raw material for a series of transformations, in patient subjectivities, medical activism, and the organization of international public health. AIDS begat new drugs, new institutions, new identities; it was the raw material that helped build today’s Global Health, which shifted the emphasis from the bilateral international public health architecture that preceded it to treatments and biotechnologies, NGOs and philanthro-capitalism. So failure here is a useful term, one that emerges against a backdrop of the industrious production of socialities, technologies and commodities. Failure is a harsh term; understandably avoided in a world where the intense competition over resources requires continuous proclamations of success. The economic crisis of 2008 intensified the competition as it inexorably led to significant budget cuts to the AIDS industry worldwide, at a time when significant funds were already committed to treatment programmes. Yet, as Cornish in this special issue points out, even the most rigorous attempts to parse published scientific studies lack analytical clarity with the result that, in fact, many interventions can be technically classified as ‘failures’. By the most

When the world catches cold: Thinking with influenza

SARS and Ebola appear as deadly epidemiological bookends for the chief subject matter of the reviewed publications: pandemic flu. SARS and Ebola are both zoonoses, but SARS emerged from the viral broth of the dense of animal/human interactions ecology of Southeast Asia, whereas the 2014 Ebola epidemic in West Africa was triggered by a random chain of transmission linking a fruit bat and a 3-year old in the Forest region of Guinea. The epidemics differed in other ways: SARS was airborne, spreading from Southeast China to Hong Kong to Toronto by jet; Ebola was touch-borne, spread through the most common gestures of care and carried from village to village to capital city by ambulance and bush-taxi. Their common denominator was fear, fuelled by viral speed and deadliness. Pandemic flu is also frightening, suspended in historical memory and always threatening to materialize. But a dramatic worldwide epidemic on the scale of the 1917–1918 ‘Spanish flu’ has never recurred, yet continues to haunt current research and public health policy debates. Nonetheless, a flu epidemic happens every year, embedding us in an autumnal (at least in Europe and North America) cycle of sniffles, sneezes and runny noses (and vaccination for those considered more vulnerable). At the heart of the matter then, lies the question of the fear of an unforeseeable, potentially cataclysmic event lurking behind the regular recurrence of what most of us experience as a benign event. Caduff, Keck and MacPhail all write against more sensationalistic accounts of pandemic flu with their dramatic tropes of virus hunters and looming catastrophe, seeking rather to demystify and explain in these ethnographies of influenza research. These works constitute a collective plea for sang-froid, careful engagement with science and paying serious attention to the perspectives of people in everyday life. Together, these three monographs point out important directions for future ethnography and theoretical elaboration. Caduff constructs the narrative of his book around prophecy, arguing that it is precisely the inscrutability of science that opens up a space for scientists to make bold and conflicting declarations. At least in the case of influenza research, science does little more, it seems, than to furnish yet another set of omens (viral genes, epidemiological signs, previous outbreaks) to be parsed. On the basis of interviews with leading flu scientists and an ethnographic exploration of “preparedness”, Pandemic Prophecy expands and elaborates on the argument (set out in more condensed form in Caduff, 2014) that the threat of the next great flu pandemic creates a zone of uncertainty that allows different science-based forecasts to compete for authority in the public sphere; what Caduff calls “scientific prophecy”. The argument is deployed in an account that explores, in six chapters, the basic, or laboratory, science of influenza and the evidentiary troubles engendered by the prophetic scene. These troubles essentially concern the way in which the “prophetic scene” sets the stage for evidentiary

Au-delà des « groupes vulnérables »: contextes et dynamique de la vulnérabilité

Résumé Cet article examine des approches de la vulnérabilité en santé publique et introduit une série de 10 articles qui abordent la vulnérabilité en santé en Afrique. Nous comprenons la vulnérabilité comme étant simultanément un état et un processus. Les inégalités sociales sont évidentes dans la vulnérabilité et en accentuent trois dimensions essentielles : le niveau initial de bien-être, le degré d’exposition au risque et la capacité à gérer le risque de façon efficace. Nous mettons un accent particulier sur les interactions dynamiques qui relient le manque matériel et social, la pauvreté, l’impuissance et la mauvaise santé : les risques, ou les chocs, et leurs impacts sur la santé sont intimement connectés entre eux et se renforcent l’un l’autre dans un cycle qui, en l’absence d’interventions efficaces, accroît la vulnérabilité. Un processus inductif qui ne commence pas par une définition ou une mesure a priori de la « vulnérabilité » et qui ne présume pas de l’existence de « groupes vulnérables » définis nous a permis à la fois de réaffirmer les aspects essentiels des cadres de référence conceptuels existants, et de nous engager dans de nouvelles voies avec une littérature abordant spécifiquement la vulnérabilité et la résilience au niveau de la population, de même qu’avec une littérature – par exemple en écologie, ainsi que sur le concept de fragilité dans la recherche sur le vieillissement – à laquelle les chercheurs du domaine de la santé et de la pauvreté en Afrique ne sont peut-être pas habitués. Nous encourageons le travail conceptuel et empirique sur la vulnérabilité dans des cadres systémiques complexes. Ces perspectives privilégient les contextes et la causalité non linéaire, soutenant ainsi les analyses sur la vulnérabilité et la résilience comme étant toutes deux des marqueurs et des propriétés émergentes d’interactions dynamiques. Nous acceptons une définition fonctionnelle de la vulnérabilité et nous reconnaissons que certains groupes définissables de personnes sont plus susceptibles que d’autres de subir des dommages du fait de leur exposition à des risques en matière de santé. Mais nous suggérons que le vrai travail – tant au niveau intellectuel qu’au niveau politique – réside dans la compréhension et la réponse apportée à la dynamique, à la signification et aux relations de pouvoir qui sous-tendent les cas et les processus réels de vulnérabilité et de dommages.