Posts filed under ‘FIEBRE en el POST-VIAJE’

Treating malaria: new drugs for a new era

Lancet Infectious Diseases December 2017 V.17 N.12 P.1223–1224


Treating malaria: new drugs for a new era

G Dennis Shanks, Jörg J Möhrle

In The Lancet Infectious Diseases, Ousmane Koita and colleagues1 reported the results of a randomised, phase 2, non-inferiority clinical trial. They compared AQ-13, a next generation 4-aminoquinoline (4-AQ) compound, with artemether plus lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in 66 Malian men.

The per-protocol analysis of this well executed trial showed that both groups had similar proportions cured (28 [100%] of 28 for AQ-13 vs 31 [93·9%] of 33 for artemether plus lumefantrine; p=0·50) and non-inferiority of AQ-13 to artemether plus lumefantrine (difference −6·1%, 95% CI −14·7 to 2·4). The intention-to-treat analysis also showed that proportions cured were also similar between the groups (28 [84·8%] of 33 for AQ-13 vs 31 [93·9%] of 33 for artemether plus lumefantrine; p=0·43); however, this analysis did not show non-inferiority of AQ-13 to artemether plus lumefantrine (difference 9·1%, 95% CI −5·6 to 23·8). The study’s suboptimal number of participants was possibly due to civil military disturbances in Mali or improving malaria control in the Sahel. The data presented show AQ-13 to be efficacious in this relatively easy-to-treat population. The next challenge is to understand how well AQ-13 will treat patients who have lower or no immunity to malaria, such as African children….





Lancet Infectious Diseases December 2017 V.17 N.12 P.1266–1275

AQ-13, an investigational antimalarial, versus artemether plus lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria: a randomised, phase 2, non-inferiority clinical trial

Prof Ousmane A Koita, PhD, Lansana Sangaré, PhD, Haiyan D Miller, BS, Aliou Sissako, MD, Moctar Coulibaly, MD, Trevor A Thompson, BS, Prof Saharé Fongoro, MD, Youssouf Diarra, PharmD, Mamadou Ba, PhD, Prof Ababacar Maiga, PhD, Prof Boubakar Diallo, MD, David M Mushatt, MD, Frances J Mather, PhD, Jeffrey G Shaffer, PhD, Asif H Anwar, MD, Prof Donald J Krogstad


Chloroquine was used for malaria treatment until resistant Plasmodium falciparum was identified. Because 4-aminoquinolines with modified side chains, such as AQ-13, are active against resistant parasites, we compared AQ-13 against artemether plus lumefantrine for treatment of uncomplicated P falciparum malaria.


We did a randomised, non-inferiority trial. We screened men (≥18 years) with uncomplicated malaria in Missira (northeast Mali) and Bamako (capital of Mali) for eligibility (≥2000 asexual P falciparum parasites per μL of blood). Eligible participants were randomly assigned to either the artemether plus lumefantrine group or AQ-13 group by permuting blocks of four with a random number generator. Physicians and others caring for the participants were masked, except for participants who received treatment and the research pharmacist who implemented the randomisation and provided treatment. Participants received either 80 mg of oral artemether and 480 mg of oral lumefantrine twice daily for 3 days or 638·50 mg of AQ-13 base (two oral capsules) on days 1 and 2, and 319·25 mg base (one oral capsule) on day 3. Participants were monitored for parasite clearance (50 μL blood samples twice daily at 12 h intervals until two consecutive negative samples were obtained) and interviewed for adverse events (once every day) as inpatients during week 1. During the 5-week outpatient follow-up, participants were examined for adverse events and recurrent infection twice per week. All participants were included in the intention-to-treat analysis and per-protocol analysis, except for those who dropped out in the per-protocol analysis. The composite primary outcome was clearance of asexual parasites and fever by day 7, and absence of recrudescent infection by parasites with the same molecular markers from days 8 to 42 (defined as cure). Non-inferiority was considered established if the proportion of patients who were cured was higher for artemether plus lumefantrine than for AQ-13 and the upper limit of the 95% CI was less than the non-inferiority margin of 15%. This trial is registered at, number NCT01614964.


Between Aug 6 and Nov 18, 2013, and between Sept 18 and Nov 20, 2015, 66 Malian men with uncomplicated malaria were enrolled. 33 participants were randomly assigned to each group. There were no serious adverse events (grade 2–4) and asexual parasites were cleared by day 7 in both groups. 453 less-severe adverse events (≤grade 1) were reported: 214 in the combination group and 239 in the AQ-13 group. Two participants withdrew from the AQ-13 group after parasite clearance and three were lost to follow-up. In the artemether plus lumefantrine group, two participants had late treatment failures (same markers as original isolates). On the basis of the per-protocol analysis, the AQ-13 and artemether plus lumefantrine groups had similar proportions cured (28 [100%] of 28 vs 31 [93·9%] of 33; p=0·50) and AQ-13 was not inferior to artemether plus lumefantrine (difference −6·1%, 95% CI −14·7 to 2·4). Proportions cured were also similar between the groups in the intention-to-treat analysis (28 of 33, 84·8% for AQ-13 vs 31 of 33, 93·9% for artemether and lumefantrine; p=0·43) but the upper bound of the 95% CI exceeded the 15% non-inferiority margin (difference 9·1%, 95% CI −5·6 to 23·8).


The per-protocol analysis suggested non-inferiority of AQ-13 to artemether plus lumefantrine. By contrast, the intention-to-treat analysis, which included two participants who withdrew and three who were lost to follow-up from the AQ-13 group, did not meet the criterion for non-inferiority of AQ-13, although there were no AQ-13 treatment failures. Studies with more participants (and non-immune participants) are needed to decide whether widespread use of modified 4-aminoquinolones should be recommended.


US Food and Drug Administration Orphan Product Development, National Institutes of Health, US Centers for Disease Control and Prevention, Burroughs-Wellcome Fund, US State Department, and WHO.





November 24, 2017 at 8:35 am

An update on Zika virus infection.  

Lancet  November 4, 2017 V.390 N.10.107 P.2099-2109


Prof David Baud, MD, Prof Duane J Gubler, ScD, Bruno Schaub, MD, Marion C Lanteri, PhD, Didier Musso, MD


The epidemic history of Zika virus began in 2007, with its emergence in Yap Island in the western Pacific, followed in 2013–14 by a larger epidemic in French Polynesia, south Pacific, where the first severe complications and non-vector-borne transmission of the virus were reported.

Zika virus emerged in Brazil in 2015 and was declared a national public health emergency after local researchers and physicians reported an increase in microcephaly cases.

In 2016, WHO declared the recent cluster of microcephaly cases and other neurological disorders reported in Brazil a global public health emergency. Similar clusters of microcephaly cases were also observed retrospectively in French Polynesia in 2014.

In 2015–16, Zika virus continued its spread to cause outbreaks in the Americas and the Pacific, and the first outbreaks were reported in continental USA, Africa, and southeast Asia.

Non-vector-borne transmission was confirmed and Zika virus was established as a cause of severe neurological complications in fetuses, neonates, and adults. This Review focuses on important updates and gaps in the knowledge of Zika virus as of early 2017.


November 3, 2017 at 8:20 am

Pregnant Women Hospitalized with Chikungunya Virus Infection, Colombia, 2015

Emerging Infectious Diseases November 2017 V.23 N.11

Maria Escobar, Albaro J. Nieto, Sara Loaiza-Osorio, Juan S. Barona, and Fernando Rosso

Fundación Clínica Valle del Lili, Cali, Colombia (M. Escobar, A.J. Nieto, S. Loaiza-Osorio, F. Rosso); Icesi University, Cali (M. Escobar, A.J. Nieto, J.S. Barona, F. Rosso)

In 2015 in Colombia, 60 pregnant women were hospitalized with chikungunya virus infections confirmed by reverse transcription PCR.

Nine of these women required admission to the intensive care unit because of sepsis with hypoperfusion and organ dysfunction; these women met the criteria for severe acute maternal morbidity. No deaths occurred.

Fifteen women delivered during acute infection; some received tocolytics to delay delivery until after the febrile episode and prevent possible vertical transmission. As recommended by a pediatric neonatologist, 12 neonates were hospitalized to rule out vertical transmission; no clinical findings suggestive of neonatal chikungunya virus infection were observed.

With 36 women (60%), follow-up was performed 1 year after acute viremia; 13 patients had arthralgia in >2 joints (a relapse of infection).

Despite disease severity, pregnant women with chikungunya should be treated in high-complexity obstetric units to rule out adverse outcomes. These women should also be followed up to treat potential relapses.


October 18, 2017 at 8:27 am

Specific Biomarkers Associated With Neurological Complications and Congenital Central Nervous System Abnormalities From Zika Virus–Infected Patients in Brazil

Journal of Infectious Diseases July 15, 2017 V.216 N.2 P.172–181

Yiu-Wing Kam; Juliana Almeida Leite; Fok-Moon Lum; Jeslin J L Tan; Bernett Lee …


Zika virus (ZIKV) infections have been linked to different levels of clinical outcomes, ranging from mild rash and fever to severe neurological complications and congenital malformations.


We investigated the clinical and immunological response, focusing on the immune mediators profile in 95 acute ZIKV-infected adult patients from Campinas, Brazil. These patients included 6 pregnant women who later delivered during the course of this study. Clinical observations were recorded during hospitalization. Levels of 45 immune mediators were quantified using multiplex microbead-based immunoassays.


Whereas 11.6% of patients had neurological complications, 88.4% displayed mild disease of rash and fever. Several immune mediators were specifically higher in ZIKV-infected patients, and levels of interleukin 10, interferon gamma-induced protein 10 (IP-10), and hepatocyte growth factor differentiated between patients with or without neurological complications. Interestingly, higher levels of interleukin 22, monocyte chemoattractant protein 1, TNF-α, and IP-10 were observed in ZIKV-infected pregnant women carrying fetuses with fetal growth–associated malformations. Notably, infants with congenital central nervous system deformities had significantly higher levels of interleukin 18 and IP-10 but lower levels of hepatocyte growth factor than those without such abnormalities born to ZIKV-infected mothers.


This study identified several key markers for the control of ZIKV pathogenesis. This will allow a better understanding of the molecular mechanisms of ZIKV infection in patients.


September 27, 2017 at 8:50 am

Dengue Virus 1 Outbreak in Buenos Aires, Argentina, 2016

Emerging Infectious Diseases October 2017 V.23 N.10

Estefanía Tittarelli, Silvina B. Lusso, Stephanie Goya, Gabriel L. Rojo, Mónica I. Natale, Mariana Viegas, Alicia S. Mistchenko, and Laura E. Valinotto

Hospital de Niños “Ricardo Gutiérrez” Buenos Aires, Argentina (E. Tittarelli, S.B. Lusso, S. Goya, G.L. Rojo, M.I. Natale, M. Viegas, A.S. Mistchenko, L.E. Valinotto); CONICET, Buenos Aires (E. Tittarelli, S. Goya, M. Viegas, L.E. Valinotto); Comisión de Investigaciones Científicas de la Provincia de Buenos Aires, Buenos Aires (A.S. Mistchenko).


The largest outbreak of dengue in Buenos Aires, Argentina, occurred during 2016. Phylogenetic, phylodynamic, and phylogeographic analyses of 82 samples from dengue patients revealed co-circulation of 2 genotype V dengue virus lineages, suggesting that this virus has become endemic to the Buenos Aires metropolitan area.


September 24, 2017 at 10:56 am

Editor’s Choice: Coinfection With Zika and Dengue-2 Viruses in a Traveler Returning From Haiti, 2016: Clinical Presentation and Genetic Analysis

Clinical Infectious Diseases January 1, 2017 V.64 N.1 P.72-75


Nicole M. Iovine, John Lednicky, Kartikeya Cherabuddi, Hannah Crooke, Sarah K. White, Julia C. Loeb, Eleonora Cella, Massimo Ciccozzi, Marco Salemi, and J. Glenn Morris, Jr

1Division of Infectious Diseases, Department of Medicine, College of Medicine

2Emerging Pathogens Institute

3Department of Environmental and Global Health, College of Public Health and Health Professions

4Department of Epidemiology, College of Public Health and Health Professions

5Department of Pathology, Immunology and Laboratory Sciences, College of Medicine, University of Florida, Gainesville

6Department of Infectious Parasitic and Immunomediated Diseases, Reference Centre on Phylogeny, Molecular Epidemiology and Microbial Evolution/Epidemiology Unit, Istituto Superiore di Sanita, Rome, Italy

Zika virus and dengue virus serotype 2 were isolated from a patient with travel to Haiti who developed fever, rash, arthralgias, and conjunctivitis. The infecting Zika virus was related to Venezuelan and Brazilian strains but evolved along a lineage originating from strains isolated in 2014 in the same region of Haiti.


August 19, 2017 at 10:26 am

EDITORIAL – Oropuche virus: A virus present but ignored

Rev.MVZ Córdoba 20(3):4675-4676, 2015

Virus de Oropuche: Un virus ignorado pero presente

El virus de Oropouche deriva su nombre de la localidad de Vegas de Oropuche, la cual se encuentra en la isla de Trinidad y Tobago, en donde fue detectado en 1955 en un paciente febril y en mosquitos Coquilletidia venezuelenzis.

El virus de Oropouche es prevalente en muchas regiones de América del Sur y del Caribe.

En el ciclo silvestre, el virus tiene varios mosquitos vectores: Culicoides paraensis, Coquilletidia venezuelenzis y Aedes serratus.

Los mamíferos silvestres son picados por estos mosquitos y aumentan las viremias, como en el oso perezoso (Bradypus tridactiyus), primates (Aloutta sanguinus) y roedores entre otros.

En el ciclo urbano los vectores son mosquitos Culicoides paraensis y Culex quinquefasciatus, ambos muy comunes en los ambientes tropicales de Colombia …


August 16, 2017 at 2:02 pm

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