Journal Article > ResearchFull Text
Trans R Soc Trop Med Hyg. 2007 August 1; Volume 101 (Issue 8); DOI:10.1016/j.trstmh.2007.02.020
van Griensven J, De Naeyer L, Mushi T, Ubarijoro S, Gashumba D, et al.
Trans R Soc Trop Med Hyg. 2007 August 1; Volume 101 (Issue 8); DOI:10.1016/j.trstmh.2007.02.020
This study was conducted among individuals placed on WHO-recommended first-line antiretroviral therapy (ART) at two urban health centres in Kigali, Rwanda, in order to determine (a) the overall prevalence of lipodystrophy and (b) the risk factors for lipoatropy. Consecutive individuals on ART for >1 year were systematically subjected to a standardised case definition-based questionnaire and clinical assessment. Of a total of 409 individuals, 370 (90%) were on an ART regimen containing stavudine (d4T), whilst the rest were receiving a zidovudine (AZT)-containing regimen. Lipodystrophy was apparent in 140 individuals (34%), of whom 40 (9.8%) had isolated lipoatrophy, 20 (4.9%) had isolated lipohypertrophy and 80 (19.6%) had mixed patterns. Fifty-six percent of patients reported the effects as disturbing. The prevalence of lipoatrophy was more than three times higher when taking d4T compared with AZT-containing regimens (31.4% vs. 10.3%). Being female, d4T-based ART, baseline body mass index >or=25 kg/m(2) or baseline CD4 count >or=150 cells/microl and increasing duration of ART were all significantly associated with lipoatrophy. Lipoatrophy appears to be an important long-term complication of WHO-recommended first-line ART regimens. These data highlight the urgent need for access to more affordable and less toxic ART regimens in resource-limited settings.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2014 August 7; Volume 8 (Issue 8); e3053.; DOI:10.1371/journal.pntd.0003053
Burza S, Mahajan R, Singh A, van Griensven J, Pandey K, et al.
PLoS Negl Trop Dis. 2014 August 7; Volume 8 (Issue 8); e3053.; DOI:10.1371/journal.pntd.0003053
Visceral Leishmaniasis (VL; also known as kala-azar) is an ultimately fatal disease endemic in the Indian state of Bihar, while HIV/AIDS is an emerging disease in this region. A 2011 observational cohort study conducted in Bihar involving 55 VL/HIV co-infected patients treated with 20-25 mg/kg intravenous liposomal amphotericin B (AmBisome) estimated an 85.5% probability of survival and a 26.5% probability of VL relapse within 2 years. Here we report the long-term field outcomes of a larger cohort of co-infected patients treated with this regimen between 2007 and 2012.
Journal Article > ResearchFull Text
PLOS One. 2017 June 30; Volume 12 (Issue 6); DOI:10.1371/journal.pone.0180070
Ingelbeen B, Bah EI, Decroo T, Balde I, Nordenstedt H, et al.
PLOS One. 2017 June 30; Volume 12 (Issue 6); DOI:10.1371/journal.pone.0180070
Non-cases are suspect Ebola Virus Disease (EVD) cases testing negative by EVD RT-PCR after admission to an Ebola Treatment Centre (ETC). Admitting non-cases to an ETC prompts concerns on case- and workload in the ETC, risk for nosocomial EVD infection, and delays in diagnosis and disease-specific treatment. We retrospectively analysed characteristics, outcomes and determinants of death of EVD cases and non-cases admitted to the Conakry ETC in Guinea between 03/2014 and 09/2015. Of the 2362 admitted suspects who underwent full confirmatory PCR testing, 1540 (65.2%) were non-cases; among them 727 needed repeated confirmatory PCR testing resulting in 2.5 days (average) in the ETC isolation ward. Twenty-one patients tested positive on the repeat test, most in a period of flawed sampling for the initial test and none after introduction of PCR confirmation with geneXpert. No readmissions following nosocomial EVD infection were recorded. No combination of symptoms yielded acceptable sensitivity and specificity to allow differentiating confirmed from non-cases. Symptoms as ocular bleeding/redness have high specificity, but limited usefulness as not common. Admission delay and age distribution were not different for both groups. In total, 98 (20.6%) of 475 deaths in the ETC were non-cases. Most died within 24 hours after admission. Living in Conakry (aOR 1.78 (1.08-2.96)) was the strongest risk factor for death. Weeks with higher admission load had lower case fatality among non-cases, probably because more acute (and treatable) illnesses of contacts of known cases were admitted. These findings show high numbers of potentially critically ill non-cases need to be considered when setting up triage and referral of EVD suspect cases. Symptoms and risk factors alone do not allow differentiating the non-cases. Integration of highly-sensitive EVD diagnostic methods with short turnaround time in the triage of peripheral hospitals and dropping the systematic 2nd PCR for symptomatic early presenters could limit delays in access to adapted care of cases and seriously ill non-cases. Whether feasible without compromising outbreak control, and under which conditions, should be further assessed.
Journal Article > CommentaryFull Text
Public Health Action. 2014 September 21; Volume 4 (Issue 3); DOI:10.5588/pha.14.0028
Zachariah R, Kumar AMV, Reid A, Van der Bergh R, Isaakidis P, et al.
Public Health Action. 2014 September 21; Volume 4 (Issue 3); DOI:10.5588/pha.14.0028
Journal Article > ResearchFull Text
PLOS One. 2017 June 5; Volume 12 (Issue 6); e0178996.; DOI:10.1371/journal.pone.0178996
Abongomera C, Ritmeijer KKD, Vogt F, Buyze J, Mekonnen Z, et al.
PLOS One. 2017 June 5; Volume 12 (Issue 6); e0178996.; DOI:10.1371/journal.pone.0178996
BACKGROUND
In Ethiopia, case fatality rates among subgroups of visceral leishmaniasis (VL) patients are high. A clinical prognostic score for death in VL patients could contribute to optimal management and reduction of these case fatality rates. We aimed to identify predictors of death from VL, and to develop and externally validate a clinical prognostic score for death in VL patients, in a high HIV co-infection burden area in Ethiopia.
METHODOLOGY/PRINCIPAL FINDINGS
We conducted a retrospective cohort study in north west Ethiopia. Predictors with an adjusted likelihood ratio ≥1.5 or ≤0.67 were retained to calculate the predictor score. The derivation cohort consisted of 1686 VL patients treated at an upgraded health center and the external validation cohort consisted of 404 VL patients treated in hospital. There were 99 deaths in the derivation cohort and 53 deaths in the external validation cohort. The predictors of death were: age >40 years (score +1); HIV seropositive (score +1); HIV seronegative (score -1); hemoglobin ≤6.5 g/dl (score +1); bleeding (score +1); jaundice (score +1); edema (score +1); ascites (score +2) and tuberculosis (score +1). The total predictor score per patient ranged from -1 to +5. A score of -1, indicated a low risk of death (1.0%), a score of 0 an intermediate risk of death (3.8%) and a score of +1 to +5, a high risk of death (10.4–85.7%). The area under the receiver operating characteristic curve was 0.83 (95% confidence interval: 0.79–0.87) in derivation, and 0.78 (95% confidence interval: 0.72–0.83) in external validation.
CONCLUSIONS/SIGNIFICANCE
The overall performance of the score was good. The score can enable the early detection of VL cases at high risk of death, which can inform operational, clinical management guidelines, and VL program management. Implementation of focused strategies could contribute to optimal management and reduction of the case fatality rates.
In Ethiopia, case fatality rates among subgroups of visceral leishmaniasis (VL) patients are high. A clinical prognostic score for death in VL patients could contribute to optimal management and reduction of these case fatality rates. We aimed to identify predictors of death from VL, and to develop and externally validate a clinical prognostic score for death in VL patients, in a high HIV co-infection burden area in Ethiopia.
METHODOLOGY/PRINCIPAL FINDINGS
We conducted a retrospective cohort study in north west Ethiopia. Predictors with an adjusted likelihood ratio ≥1.5 or ≤0.67 were retained to calculate the predictor score. The derivation cohort consisted of 1686 VL patients treated at an upgraded health center and the external validation cohort consisted of 404 VL patients treated in hospital. There were 99 deaths in the derivation cohort and 53 deaths in the external validation cohort. The predictors of death were: age >40 years (score +1); HIV seropositive (score +1); HIV seronegative (score -1); hemoglobin ≤6.5 g/dl (score +1); bleeding (score +1); jaundice (score +1); edema (score +1); ascites (score +2) and tuberculosis (score +1). The total predictor score per patient ranged from -1 to +5. A score of -1, indicated a low risk of death (1.0%), a score of 0 an intermediate risk of death (3.8%) and a score of +1 to +5, a high risk of death (10.4–85.7%). The area under the receiver operating characteristic curve was 0.83 (95% confidence interval: 0.79–0.87) in derivation, and 0.78 (95% confidence interval: 0.72–0.83) in external validation.
CONCLUSIONS/SIGNIFICANCE
The overall performance of the score was good. The score can enable the early detection of VL cases at high risk of death, which can inform operational, clinical management guidelines, and VL program management. Implementation of focused strategies could contribute to optimal management and reduction of the case fatality rates.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2014 June 26; Volume 8 (Issue 6); e2869.; DOI:10.1371/journal.pntd.0002869
Diro EGJ, Lynen L, Ritmeijer KKD, Boelaert M, Hailu ADE, et al.
PLoS Negl Trop Dis. 2014 June 26; Volume 8 (Issue 6); e2869.; DOI:10.1371/journal.pntd.0002869
Visceral Leishmaniasis (VL) is an important protozoan opportunistic disease in HIV patients in endemic areas. East Africa is second to the Indian subcontinent in the global VL caseload and first in VL-HIV coinfection rate. Because of the alteration in the disease course, the diagnostic challenges, and the poor treatment responses, VL with HIV coinfection has become a very serious challenge in East Africa today. Field experience with the use of liposomal amphotericin B in combination with miltefosine, followed by secondary prophylaxis and antiretroviral drugs, looks promising. However, this needs to be confirmed through clinical trials. Better diagnostic and follow-up methods for relapse and prediction of relapse should also be looked for. Basic research to understand the immunological interaction of the two infections may ultimately help to improve the management of the coinfection.
Journal Article > CommentaryFull Text
Clin Infect Dis. 2015 August 10; Volume 62 (Issue 1); 69-74.; DOI:10.1093/cid/civ680
van Griensven J, De Weiggheleire A, Delamou A, Smith PJ, Edwards T, et al.
Clin Infect Dis. 2015 August 10; Volume 62 (Issue 1); 69-74.; DOI:10.1093/cid/civ680
The clinical evaluation of convalescent plasma (CP) for the treatment of Ebola Virus Disease (EVD) in the current outbreak, predominantly affecting Guinea, Sierra Leone and Liberia, was prioritized by the World Health Organization in September 2014. In each of these countries, non-randomized comparative clinical trials were initiated. The Ebola-Tx trial in Conakry, Guinea enrolled 102 patients by July 7, 2015; no severe adverse reactions were noted. The Ebola-CP trial in Sierra Leone and the EVD001 trial in Liberia have included few patients. While no efficacy data are available yet, current field experience supports the safety, acceptability and feasibility of CP as EVD treatment. Longer-term follow-up as well as data from non-trial settings and evidence on the scalability of the intervention are required. CP sourced from within the outbreak is the most readily available source of anti-EVD antibodies. Until the advent of effective antivirals or monoclonal antibodies, CP merits further evaluation.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2018 May 25; Volume 12 (Issue 5); DOI:10.1371/journal.pntd.0006527
Abongomera C, Diro EGJ, de Lima Pereira A, Buyze J, Stille K, et al.
PLoS Negl Trop Dis. 2018 May 25; Volume 12 (Issue 5); DOI:10.1371/journal.pntd.0006527
North-west Ethiopia faces the highest burden world-wide of visceral leishmaniasis (VL) and HIV co-infection. VL-HIV co-infected patients have higher (initial) parasitological failure and relapse rates than HIV-negative VL patients. Whereas secondary prophylaxis reduces the relapse rate, parasitological failure rates remain high with the available antileishmanial drugs, especially when administered as monotherapy. We aimed to determine the initial effectiveness (parasitologically-confirmed cure) of a combination of liposomal amphotericin B (AmBisome) and miltefosine for treatment of VL in HIV co-infected patients.
Journal Article > ResearchAbstract
Trans R Soc Trop Med Hyg. 2010 December 1; Volume 104 (Issue 12); DOI:10.1016/j.trstmh.2010.08.016
van Griensven J, Zachariah R, Mugabo J, Reid AJ
Trans R Soc Trop Med Hyg. 2010 December 1; Volume 104 (Issue 12); DOI:10.1016/j.trstmh.2010.08.016
This study was conducted among 609 adults on stavudine-based antiretroviral treatment (ART) for at least one year at health center level in Kigali, Rwanda to (a) determine the proportion who manifest weight loss after one year of ART (b) examine the association between such weight loss and a number of variables, namely: lipoatrophy, virological failure, adherence and on-treatment CD4 count and (c) assess the validity and predictive values of weight loss to identify patients with lipoatrophy. Weight loss after the first year of ART was seen in 62% of all patients (median weight loss 3.1 kg/year). In multivariate analysis, weight loss was significantly associated with treatment-limiting lipoatrophy (adjusted effect/kg/year -2.0 kg, 95% confidence interval -0.6;-3.4 kg; P<0.01). No significant association was found with virological failure or adherence. Higher on-treatment CD4 cell counts were protective against weight loss. Weight loss that was persistent, progressive and/or chronic was predictive of lipoatrophy, with a sensitivity and specificity of 72% and 77%, and positive and negative predictive values of 30% and 95%. In low-income countries, measuring weight is a routine clinical procedure that could be used to filter out individuals with lipoatrophy on stavudine-based ART, after alternative causes of weight loss have been ruled out.
Journal Article > Case Report/SeriesFull Text
Clin Infect Dis. 2024 January 9; Online ahead of print; ciae002.; DOI:10.1093/cid/ciae002
van Griensven J, van Henten S, Kibret A, Kassa M, Beyene H, et al.
Clin Infect Dis. 2024 January 9; Online ahead of print; ciae002.; DOI:10.1093/cid/ciae002
BACKGROUND
HIV patients with recurrent visceral leishmaniasis (VL) could potentially drive Leishmania transmission in areas with anthroponotic transmission such as East-Africa, but studies are lacking. Leishmania parasitemia has been used as proxy for infectiousness.
METHODS
This study is nested within the PreLeish prospective cohort study, following a total of 490 HIV infected individuals free of VL at enrollment for up to 24-37 months in North-West Ethiopia. Blood Leishmania PCR was done systematically. This case series reports on ten HIV-coinfected individuals with chronic VL (≥3 VL episodes during follow-up) for up to 37 months, and three individuals with asymptomatic Leishmania infection for up to 24 months.
RESULTS
All ten chronic VL cases were male, on antiretroviral treatment, with 0-11 relapses before enrollment. Median baseline CD4 counts were 82 cells/µL. They displayed three to six VL treatment episodes over a period up to 37 months. Leishmania blood PCR levels were strongly positive for almost the entire follow-up time (median Ct value 26 (IQR 23-30), including during periods between VL treatment. Additionally, we describe three HIV-infected individuals with asymptomatic Leishmania infection and without VL history, with equally strong Leishmania parasitemia over a period of up to 24 months without developing VL. All were on antiretroviral treatment at enrollment, with baseline CD4 counts ranging from 78 to 350 cells/µL.
CONCLUSION
These are the first data on chronic parasitemia in HIV-infected individuals from L donovani endemic areas. HIV patients with asymptomatic and symptomatic Leishmania infection could potentially be highly infectious and constitute Leishmania superspreaders. Xenodiagnosis studies are required to confirm infectiousness.
HIV patients with recurrent visceral leishmaniasis (VL) could potentially drive Leishmania transmission in areas with anthroponotic transmission such as East-Africa, but studies are lacking. Leishmania parasitemia has been used as proxy for infectiousness.
METHODS
This study is nested within the PreLeish prospective cohort study, following a total of 490 HIV infected individuals free of VL at enrollment for up to 24-37 months in North-West Ethiopia. Blood Leishmania PCR was done systematically. This case series reports on ten HIV-coinfected individuals with chronic VL (≥3 VL episodes during follow-up) for up to 37 months, and three individuals with asymptomatic Leishmania infection for up to 24 months.
RESULTS
All ten chronic VL cases were male, on antiretroviral treatment, with 0-11 relapses before enrollment. Median baseline CD4 counts were 82 cells/µL. They displayed three to six VL treatment episodes over a period up to 37 months. Leishmania blood PCR levels were strongly positive for almost the entire follow-up time (median Ct value 26 (IQR 23-30), including during periods between VL treatment. Additionally, we describe three HIV-infected individuals with asymptomatic Leishmania infection and without VL history, with equally strong Leishmania parasitemia over a period of up to 24 months without developing VL. All were on antiretroviral treatment at enrollment, with baseline CD4 counts ranging from 78 to 350 cells/µL.
CONCLUSION
These are the first data on chronic parasitemia in HIV-infected individuals from L donovani endemic areas. HIV patients with asymptomatic and symptomatic Leishmania infection could potentially be highly infectious and constitute Leishmania superspreaders. Xenodiagnosis studies are required to confirm infectiousness.