Journal Article > CommentaryFull Text
J Infect Dis. 19 August 2023; online ahead of print; jiad354.; DOI:10.1093/infdis/jiad354
Sprecher A, Cross RW, Marzi A, Martins KA, Wolfe D, et al.
J Infect Dis. 19 August 2023; online ahead of print; jiad354.; DOI:10.1093/infdis/jiad354
Although there are now approved treatments and vaccines for Ebola virus disease (EVD), the case fatality of EVD remains unacceptably high even when treated with the newly approved therapeutics; furthermore, these countermeasures are not expected to be effective against disease caused by other filoviruses. A meeting of subject matter experts from public health, research, and countermeasure development agencies and manufacturers was held during the 10th International Filovirus Symposium to discuss strategies to address these gaps, including how newer countermeasures could be advanced for field readiness. Several investigational therapeutics, vaccine candidates, and combination strategies were presented. In all, a common theme emerged: the greatest challenge to completing development was the implementation of well-designed clinical trials of safety and efficacy during filovirus disease outbreaks. These outbreaks are usually of short duration, providing but a brief opportunity for trials to be launched, and have too few cases to allow for full enrollment during a single outbreak, so clinical trials will necessarily need to span multiple outbreaks which may occur in a number of at-risk countries. Preparing for this will require agreed-upon common protocols for trials intended to bridge multiple outbreaks across all at-risk countries. A multi-national research consortium including, and led by, at-risk countries would be an ideal mechanism to negotiate agreement on protocol design and coordinate preparation. Discussion participants recommended a follow-up meeting be held in Africa with national public health and research agencies from at-risk countries to establish such a consortium.
Journal Article > CommentarySubscription Only
Lancet Infect Dis. 18 August 2023; Volume S1473-3099 (Issue 23); 00506-6.; DOI:10.1016/S1473-3099(23)00506-6
Kofman AD, Haberling DL, Mbuyi G, Martel LD, Whitesell AN, et al.
Lancet Infect Dis. 18 August 2023; Volume S1473-3099 (Issue 23); 00506-6.; DOI:10.1016/S1473-3099(23)00506-6
Journal Article > Short ReportFull Text
Morbidity and Mortality Weekly Report. 14 November 2014; Volume 63 (Issue 46); 1082-6.
Nyenswah TG, Fahnbulleh M, Massaquoi M, Nagbe T, Bawo L, et al.
Morbidity and Mortality Weekly Report. 14 November 2014; Volume 63 (Issue 46); 1082-6.
On March 21, 2014, the Guinea Ministry of Health reported the outbreak of an illness characterized by fever, severe diarrhea, vomiting and a high fatality rate (59%), leading to the first known epidemic of Ebola virus disease (Ebola) in West Africa and the largest and longest Ebola epidemic in history. As of November 2, Liberia had reported the largest number of cases (6,525) and deaths (2,697) among the three affected countries of West Africa with ongoing transmission (Guinea, Liberia, and Sierra Leone). The response strategy in Liberia has included management of the epidemic through an incident management system (IMS) in which the activities of all partners are coordinated. Within the IMS, key strategies for epidemic control include surveillance, case investigation, laboratory confirmation, contact tracing, safe transportation of persons with suspected Ebola, isolation, infection control within the health care system, community engagement, and safe burial. This report provides a brief overview of the progression of the epidemic in Liberia and summarizes the interventions implemented.
Journal Article > ResearchFull Text
Trop Med Int Health. 1 October 2006; Volume 11 (Issue 10); DOI:10.1111/j.1365-3156.2006.01710.x
Swarthout TD, van den Broek IVF, Kayembe G, Montgomery JM, Pota H, et al.
Trop Med Int Health. 1 October 2006; Volume 11 (Issue 10); DOI:10.1111/j.1365-3156.2006.01710.x
We undertook a trial of artesunate + amodiaquine (AS + AQ) and artesunate + sulphadoxine-pyrimethamine (AS + SP) in 180 children of age 6-59 months with uncomplicated malaria in Democratic Republic of Congo. Children were randomly allocated to receive 3 days observed treatment of AS + AQ (n = 90) or 3 days of AS + SP (n = 90). Primary efficacy outcomes were 28-day parasite recurrence rates, and recrudescence rates were adjusted by genotyping to distinguish new infection and recrudescence. In addition, we determined the prevalence of molecular markers of resistance to sulphadoxine and pyrimethamine. Day 28 parasite recurrence rates were 16.9% (14/83; 95% CI: 9.5-26.7) in the AS + AQ group and 34.6% (28/81; 95% CI: 24.3-46.0) in the AS + SP group (P = 0.009). After PCR correction, recrudescence rates were 6.7% (5/74; 95% CI: 2.2-15.1) for AS + AQ and 19.7% (13/66; 95% CI: 10.9-31.3) for AS + SP (P = 0.02). There was no significant difference between the two arms in time to parasite clearance, fever clearance and gametocyte clearance. Parasite genotyping showed high frequencies of dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) molecular SP-resistance markers, with 57% of the samples showing more than three mutations linked to SP resistance, and 27% with triple-dhfr/double-dhps haplotype, confirming that SP treatment failure rates are likely to be high. AS + AQ had significantly higher efficacy than AS + SP. These results contributed to the subsequent change to AS + AQ as first-line regimen in the country. Efforts to properly implement the new protocol and maintain adherence at acceptable levels should include health staff and patient sensitization. The 6.8% recrudescence rate indicates that AS + AQ should be monitored closely until a more effective artemisinin combination therapy regimen is needed and can be introduced.
Journal Article > ResearchFull Text
Trans R Soc Trop Med Hyg. 1 July 2005; Volume 99 (Issue 7); 548-554.; DOI:10.1016/j.trstmh.2004.10.003
Hamour S, Melaku Y, Keus K, Wambugu J, Atkin S, et al.
Trans R Soc Trop Med Hyg. 1 July 2005; Volume 99 (Issue 7); 548-554.; DOI:10.1016/j.trstmh.2004.10.003
Both northern and southern Sudan are deploying artemisinin-based combinations against uncomplicated Plasmodium falciparum malaria (artesunate+sulfadoxine-pyrimethamine [AS+SP] in the north, artesunate+amodiaquine [AS+AQ] in the south). In 2003, we tested the efficacy of 3 day AS+SP and AS+AQ regimens in vivo in the isolated, seasonally endemic Nuba Mountains region (the first study of AS combinations in southern Sudan). We also analysed pre-treatment blood samples for mutations at the P. falciparum chloroquine transporter (Pfcrt) gene (associated with CQ resistance), and at the dihydrofolate reductase (Dhfr) gene (associated with pyrimethamine resistance). Among 161 randomized children under 5 years, PCR-corrected cure rates after 28 days were 91.2% (52/57, 95% CI 80.7-97.1) for AS+SP and 92.7% (51/55, 95% CI 82.4-98.0) for AS+AQ, with equally rapid parasite and fever clearance. The Pfcrt K76T mutation occurred in 90.0% (144/160) of infections, suggesting CQ would work poorly in this region. Overall, 82.5% (132/160) carried mutations at Dhfr (N51I, C59R or S108N, but not I164L), but triple mutants (more predictive of in vivo SP failure) were rare (3.1%). CQ use should be rapidly discontinued in this region. SP resistance may propagate rapidly, and AS+AQ is likely to be a better long-term option, provided AQ use is limited to the combination.