Journal Article > ResearchFull Text
J Infect Dis. 16 December 2024; Volume 230 (Issue 6); e1235-e1244.; DOI:10.1093/infdis/jiae221
Cortes-Azuero O, Lefrancq N, Nikolay B, McKee C, Cappelle J, et al.
J Infect Dis. 16 December 2024; Volume 230 (Issue 6); e1235-e1244.; DOI:10.1093/infdis/jiae221
BACKGROUND
Nipah virus (NiV), a highly lethal virus in humans, circulates in Pteropus bats throughout South and Southeast Asia. Difficulty in obtaining viral genomes from bats means we have a poor understanding of NiV diversity.
METHODS
We develop phylogenetic approaches applied to the most comprehensive collection of genomes to date (N = 257, 175 from bats, 73 from humans) from 6 countries over 22 years (1999–2020). We divide the 4 major NiV sublineages into 15 genetic clusters. Using Approximate Bayesian Computation fit to a spatial signature of viral diversity, we estimate the presence and the average size of genetic clusters per area.
RESULTS
We find that, within any bat roost, there are an average of 2.4 co-circulating genetic clusters, rising to 5.5 clusters at areas of 1500–2000 km2. We estimate that each genetic cluster occupies an average area of 1.3 million km2 (95% confidence interval [CI], .6–2.3 million km2), with 14 clusters in an area of 100 000 km2 (95% CI, 6–24 km2). In the few sites in Bangladesh and Cambodia where genomic surveillance has been concentrated, we estimate that most clusters have been identified, but only approximately 15% of overall NiV diversity has been uncovered.
CONCLUSIONS
Our findings are consistent with entrenched co-circulation of distinct lineages, even within roosts, coupled with slow migration over larger spatial scales.
Journal Article > CommentaryFull Text
J Infect Dis. 16 December 2024; Volume 230 (Issue 6); e1375-1384.; DOI:10.1093/infdis/jiae413
Chu WY, Verrest L, Younis BM, Musa AM, Mbui J, et al.
J Infect Dis. 16 December 2024; Volume 230 (Issue 6); e1375-1384.; DOI:10.1093/infdis/jiae413
Treatment regimens for post-kala-azar dermal leishmaniasis (PKDL) are usually extrapolated from those for visceral leishmaniasis (VL), but drug pharmacokinetics (PK) can differ due to disease-specific variations in absorption, distribution, and elimination. This study characterized PK differences in paromomycin and miltefosine between 109 PKDL and 264 VL patients from eastern Africa. VL patients showed 0.55-fold (95%CI: 0.41-0.74) lower capacity for paromomycin saturable reabsorption in renal tubules, and required a 1.44-fold (1.23-1.71) adjustment when relating renal clearance to creatinine-based eGFR. Miltefosine bioavailability in VL patients was lowered by 69% (62-76) at treatment start. Comparing PKDL to VL patients on the same regimen, paromomycin plasma exposures were 0.74-0.87-fold, while miltefosine exposure until the end of treatment day was 1.4-fold. These pronounced PK differences between PKDL and VL patients in eastern Africa highlight the challenges of directly extrapolating dosing regimens from one leishmaniasis presentation to another.
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 > ResearchFull Text
J Infect Dis. 1 June 2005; Volume 191 (Issue 11); DOI:10.1086/429929
Schmid C, Richer M, Bilenge CM, Josenando T, Chappuis F, et al.
J Infect Dis. 1 June 2005; Volume 191 (Issue 11); DOI:10.1086/429929
BACKGROUND: Treatment of late-stage human African trypanosomiasis (HAT) with melarsoprol can be improved by shortening the regimen. A previous trial demonstrated the safety and efficacy of a 10-day treatment schedule. We demonstrate the effectiveness of this schedule in a noncontrolled, multinational drug-utilization study. METHODS: A total of 2020 patients with late-stage HAT were treated with the 10-day melarsoprol schedule in 16 centers in 7 African countries. We assessed outcome on the basis of major adverse events and the cure rate after treatment and during 2 years of follow-up. RESULTS: The cure rate 24 h after treatment was 93.9%; 2 years later, it was 86.2%. However, 49.3% of patients were lost to follow-up. The overall fatality rate was 5.9%. Of treated patients, 8.7% had an encephalopathic syndrome that was fatal 45.5% of the time. The rate of severe bullous and maculopapular eruptions was 0.8% and 6.8%, respectively. CONCLUSIONS: The 10-day treatment schedule was well implemented in the field and was effective. It reduces treatment duration, drug amount, and hospitalization costs per patient, and it increases treatment-center capacity. The shorter protocol has been recommended by the International Scientific Council for Trypanosomiasis Research and Control for the treatment of late-stage HAT caused by Trypanosoma brucei gambiense.
Journal Article > ResearchFull Text
J Infect Dis. 25 May 2016; Volume 215 (Issue 1); 64–69.; DOI:10.1093/infdis/jiw206
Muehlenbachs A, de la Rosa Vazquez O, Bausch DG, Schafer IJ, Paddock C, et al.
J Infect Dis. 25 May 2016; Volume 215 (Issue 1); 64–69.; DOI:10.1093/infdis/jiw206
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.
Journal Article > ResearchFull Text
J Infect Dis. 13 October 2014; Volume 211 (Issue 10); DOI:10.1093/infdis/jiu551
Bastard M, Sanchez-Padilla E, Hewison CCH, Hayrapetyan A, Khurkhumal S, et al.
J Infect Dis. 13 October 2014; Volume 211 (Issue 10); DOI:10.1093/infdis/jiu551
The success of the current treatment regimen for multidrug-resistant tuberculosis (MDR-TB) is poor partly due to a high defaulter rate. Many studies explored predictors of poor outcomes, but very few assessed the impact of treatment interruptions on MDR-TB treatment outcomes.
Journal Article > ResearchFull Text
J Infect Dis. 28 July 2016; Volume 214 (Issue suppl 3); S303-S307.; DOI:10.1093/infdis/jiw187
de Wit E, Kramer S, Prescott JB, Rosenke K, Falzarano D, et al.
J Infect Dis. 28 July 2016; Volume 214 (Issue suppl 3); S303-S307.; DOI:10.1093/infdis/jiw187
The development of point-of-care clinical chemistry analyzers has enabled the implementation of these ancillary tests in field laboratories in resource-limited outbreak areas. The Eternal Love Winning Africa (ELWA) outbreak diagnostic laboratory, established in Monrovia, Liberia, to provide Ebola virus and Plasmodium spp. diagnostics during the Ebola epidemic, implemented clinical chemistry analyzers in December 2014. Clinical chemistry testing was performed for 68 patients in triage, including 12 patients infected with Ebola virus and 18 infected with Plasmodium spp. The main distinguishing feature in clinical chemistry of Ebola virus-infected patients was the elevation in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyltransferase levels and the decrease in calcium. The implementation of clinical chemistry is probably most helpful when the medical supportive care implemented at the Ebola treatment unit allows for correction of biochemistry derangements and on-site clinical chemistry analyzers can be used to monitor electrolyte balance.
Journal Article > ResearchFull Text
J Infect Dis. 22 May 2015; Volume 212 (Issue 11); DOI:10.1093/infdis/jiv304
Fitzpatrick G, Vogt F, Gbabai O, Decroo T, Keane M, et al.
J Infect Dis. 22 May 2015; Volume 212 (Issue 11); DOI:10.1093/infdis/jiv304
This paper describes patient characteristics, including Ebola viral load, associated with mortality in an MSF Ebola case management centre. Out of 780 admissions between June and October 2014, 525 (67%) were positive for Ebola with a known outcome. The crude mortality rate was 51% (270/525). Ebola viral load (whole blood sample) data was available on 76% (397/525) of patients. Univariate analysis indicated viral load at admission, age, symptom duration prior to admission and distance travelled to the CMC were associated with mortality (p value<0.05). The multivariable model predicted mortality in those with a viral load at admission greater than 10 million copies per millilitre (p value<0.05, Odds Ratio>10), aged 50 years or more (p value=0.08, Odds Ratio=2) and symptom duration prior to admission less than 5 days (p value=0.14). The presence of confusion, diarrhoea and conjunctivitis were significantly higher (p value<0.05) in Ebola patients who died. These findings highlight the importance viral load at admission has on mortality outcomes and could be used to cohort cases with viral loads greater than 10 million copies into dedicated wards with more intensive medical support to further reduce mortality.
Journal Article > ResearchFull Text
J Infect Dis. 30 June 2016; Volume 214 (Issue suppl 3); S145-S152.; DOI:10.1093/infdis/jiw198
Poliquin PG, Vogt F, Kasztura M, Leung A, Deschambault Y, et al.
J Infect Dis. 30 June 2016; Volume 214 (Issue suppl 3); S145-S152.; DOI:10.1093/infdis/jiw198
BACKGROUND
Ebola viruses (EBOVs) are primarily transmitted by contact with infected body fluids. Ebola treatment centers (ETCs) contain areas that are exposed to body fluids through the care of patients suspected or confirmed to have EBOV disease. There are limited data documenting which areas/fomites within ETCs pose a risk for potential transmission. This study conducted environmental surveillance in 2 ETCs in Freetown, Sierra Leone, during the 2014–2016 West African Ebola outbreak.
METHODS
ETCs were surveyed over a 3-week period. Sites to be swabbed were identified with input from field personnel. Swab samples were collected and tested for the presence of EBOV RNA. Ebola-positive body fluid-impregnated cotton pads were serially sampled.
RESULTS
General areas of both ETCs were negative for EBOV RNA. The immediate vicinity of patients was the area most likely to be positive for EBOV RNA. Personal protective equipment became positive during patient care, but chlorine solution washes rendered them negative.
CONCLUSIONS
Personal protective equipment and patient environs do become positive for EBOV RNA, but careful attention to decontamination seems to remove it. EBOV RNA was not detected in general ward spaces. Careful attention to decontamination protocols seems to be important in minimizing the presence of EBOV RNA within ETC wards.
Ebola viruses (EBOVs) are primarily transmitted by contact with infected body fluids. Ebola treatment centers (ETCs) contain areas that are exposed to body fluids through the care of patients suspected or confirmed to have EBOV disease. There are limited data documenting which areas/fomites within ETCs pose a risk for potential transmission. This study conducted environmental surveillance in 2 ETCs in Freetown, Sierra Leone, during the 2014–2016 West African Ebola outbreak.
METHODS
ETCs were surveyed over a 3-week period. Sites to be swabbed were identified with input from field personnel. Swab samples were collected and tested for the presence of EBOV RNA. Ebola-positive body fluid-impregnated cotton pads were serially sampled.
RESULTS
General areas of both ETCs were negative for EBOV RNA. The immediate vicinity of patients was the area most likely to be positive for EBOV RNA. Personal protective equipment became positive during patient care, but chlorine solution washes rendered them negative.
CONCLUSIONS
Personal protective equipment and patient environs do become positive for EBOV RNA, but careful attention to decontamination seems to remove it. EBOV RNA was not detected in general ward spaces. Careful attention to decontamination protocols seems to be important in minimizing the presence of EBOV RNA within ETC wards.
Journal Article > ResearchFull Text
J Infect Dis. 28 August 2016; Volume 214 (Issue 9); DOI:10.1093/infdis/jiw396
Reynaldi A, Schlub TE, Piriou E, Ogolla S, Sumba OP, et al.
J Infect Dis. 28 August 2016; Volume 214 (Issue 9); DOI:10.1093/infdis/jiw396
The combination of Epstein-Barr virus (EBV) infection and high malaria exposure are risk factors for endemic Burkitt lymphoma, and evidence suggests that infants in regions of high malaria exposure have earlier EBV infection and increased EBV reactivation. Here we analysed the longitudinal antibody response to EBV in Kenyan infants with different levels of malaria exposure. We found that high malaria exposure was associated with a faster decline of maternally-derived IgG antibody to both the EBV viral capsid antigen (VCA) and Epstein-Barr virus nuclear antigen (EBNA1), followed by a more rapid rise in antibody response to EBV antigens in children from the high malaria region. In addition, we observed the long-term persistence of anti-VCA IgM responses in children from the malaria high region. More rapid decay of maternal antibodies was a major predictor of EBV infection outcome, as decay predicted time-to EBV DNA detection, independent of high and low malaria exposure.