Journal Article > Case Report/SeriesFull Text
Clin Infect Dis. 9 January 2024; 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. 9 January 2024; 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.
Journal Article > ReviewAbstract Only
Lancet Infect Dis. 1 January 2024; Volume 24 (Issue 1); e36-e46.; DOI:10.1016/S1473-3099(23)00353-5
van Griensven J, Dorlo TPC, Diro EGJ, Costa CH, Burza S
Lancet Infect Dis. 1 January 2024; Volume 24 (Issue 1); e36-e46.; DOI:10.1016/S1473-3099(23)00353-5
For the past 15 years, trials of combination therapy options for visceral leishmaniasis have been conducted with the aim of identifying effective, and safe treatment regimens that were shorter than existing monotherapy regimens and could also prevent or delay the emergence of drug resistance. Although first-line treatment currently relies on combination therapy in east Africa, this is not true in Latin America owing to disappointing trial results, with lower than expected efficacy seen for the combination treatment group. By contrast, several effective combination therapy regimens have been identified through trials on the Indian subcontinent; yet, first-line therapy is still AmBisome monotherapy as the drug is part of a free donation programme and is highly effective in this region. Achieving a short all-oral combination treatment will require new chemical entities, several of which are currently under evaluation. Future studies should systematically include pharmacological substudies to ensure optimal dosing for all patient groups. To achieve maximal impact of new combination treatments, mechanisms to ensure drug availability and access after trials should be established. Enhancing the longevity of current and novel treatments will require effective systems for early detection of emerging drug resistance.
Journal Article > CommentaryFull Text
PLoS Negl Trop Dis. 23 March 2023; Volume 17 (Issue 3); e0011188.; DOI:10.1371/journal.pntd.0011188
Boodman C, van Griensven J, Gupta N, Diro EGJ, Ritmeijer KKD
PLoS Negl Trop Dis. 23 March 2023; Volume 17 (Issue 3); e0011188.; DOI:10.1371/journal.pntd.0011188
Journal Article > ResearchFull Text
PLOS One. 5 June 2017; 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. 5 June 2017; 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. 25 May 2018; 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. 25 May 2018; 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 > ResearchFull Text
PLoS Negl Trop Dis. 26 June 2014; 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. 26 June 2014; 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.
Protocol > Research Protocol
Diro EGJ, Griensven JV, Woldegebreal T, Belew Z, Taye M, et al.
1 July 2018
2.1 OBJECTIVES
2.1.1 General objective:
To document the effectiveness, safety and feasibility of monthly PM secondary prophylaxis (PSP) in VL/HIV co-infected patients that have documented parasite clearance after VL treatment when used for prevention of VL relapse.
2.1.2 Specific objectives of the primary study period
2.1.2.1 Primary objectives
In VL/HIV co-infected patients that have documented parasite clearance after VL treatment:
- to assess the effectiveness of PSP in terms of preventing relapse and death;
- to assess the safety of PSP in terms of drug-related serious adverse events or permanent drug discontinuations due to adverse events;
- to assess the feasibility of PSP in terms of number of patients compliant to therapy
during the first year of monthly PM secondary prophylaxis.
2.1.2.2 Secondary objectives;
In VL/HIV co-infected patients that have documented parasite clearance after VL treatment:
- to assess the safety of PSP in terms of:
- drug-related non-serious adverse events
- serious adverse events (drug-related or not)
- to assess the feasibility of PSP in terms of:
- number of treatment interruptions/discontinuations,
- number of therapeutic interventions needed to treat adverse drug reactions
2.1.1 General objective:
To document the effectiveness, safety and feasibility of monthly PM secondary prophylaxis (PSP) in VL/HIV co-infected patients that have documented parasite clearance after VL treatment when used for prevention of VL relapse.
2.1.2 Specific objectives of the primary study period
2.1.2.1 Primary objectives
In VL/HIV co-infected patients that have documented parasite clearance after VL treatment:
- to assess the effectiveness of PSP in terms of preventing relapse and death;
- to assess the safety of PSP in terms of drug-related serious adverse events or permanent drug discontinuations due to adverse events;
- to assess the feasibility of PSP in terms of number of patients compliant to therapy
during the first year of monthly PM secondary prophylaxis.
2.1.2.2 Secondary objectives;
In VL/HIV co-infected patients that have documented parasite clearance after VL treatment:
- to assess the safety of PSP in terms of:
- drug-related non-serious adverse events
- serious adverse events (drug-related or not)
- to assess the feasibility of PSP in terms of:
- number of treatment interruptions/discontinuations,
- number of therapeutic interventions needed to treat adverse drug reactions
Protocol > Research Protocol
Griensven JV, Diro EGJ
1 July 2018
Aim To study the asymptomatic period preceding the onset of active VL in HIV‐infected individuals from VL endemic regions in Ethiopia as an avenue to develop an evidence‐based screen and treat strategy to prevent progression to active VL.Primary:
1. To estimate the prevalence of asymptomatic Leishmania infection .
2. To estimate the incidence rate of asymptomatic Leishmania infection.
3. To describe the evolution of Leishmania infection markers over time.
4. To estimate the incidence rate of active VL.
5. To identify risk factors associated with the development of active VL.
6. To translate these risk factors into a clinical prognostic tool to identify individuals at high risk to develop active VL within 12 months .
Secondary:
1. To identify patterns in host immune markers that are associated with asymptomatic Leishmania infection.
2. To describe the evolution of host immune markers over time.
3. To identify patterns in host immune markers that are associated with treatment failure.
4. To identify patterns in host immune markers that are associated with VL relapse.
1. To estimate the prevalence of asymptomatic Leishmania infection .
2. To estimate the incidence rate of asymptomatic Leishmania infection.
3. To describe the evolution of Leishmania infection markers over time.
4. To estimate the incidence rate of active VL.
5. To identify risk factors associated with the development of active VL.
6. To translate these risk factors into a clinical prognostic tool to identify individuals at high risk to develop active VL within 12 months .
Secondary:
1. To identify patterns in host immune markers that are associated with asymptomatic Leishmania infection.
2. To describe the evolution of host immune markers over time.
3. To identify patterns in host immune markers that are associated with treatment failure.
4. To identify patterns in host immune markers that are associated with VL relapse.
Journal Article > CommentaryFull Text
PLoS Negl Trop Dis. 17 July 2014; Volume 8 (Issue 7); e2916.; DOI:10.1371/journal.pntd.0002916
van Griensven J, Ritmeijer KKD, Lynen L, Diro EGJ
PLoS Negl Trop Dis. 17 July 2014; Volume 8 (Issue 7); e2916.; DOI:10.1371/journal.pntd.0002916
Journal Article > ResearchFull Text
Trans R Soc Trop Med Hyg. 18 March 2017; Volume 111 (Issue 1); 22-29.; DOI:10.1093/trstmh/trx009
Camara BS, Delamou A, Diro EGJ, Beavogui A, El Ayadi AM, et al.
Trans R Soc Trop Med Hyg. 18 March 2017; Volume 111 (Issue 1); 22-29.; DOI:10.1093/trstmh/trx009
BACKGROUND
The 2014/2015 Ebola outbreak was the most sustained in history. In Guinea, we compared trends in family planning, antenatal care, and institutional deliveries over the period before, during and after the outbreak.
METHODS
We carried out an ecological study involving all the health facilities during pre-Ebola (1 March 2013 to 28 February 2014), intra-Ebola (1 March 2014 to 28 February 2015) and post-Ebola (1 March to 31 July 2016) periods in Macenta district.
RESULTS
Utilization of family planning declined from a monthly average of 531 visits during the pre-Ebola period to 242 visits in the peak month of the Ebola outbreak (51% decline) but recovered in the post-Ebola period. From a monthly average of 2053 visits pre-Ebola, antenatal care visits declined by 41% during Ebola and then recovered to only 63% of the pre-Ebola level (recovery gap of 37%, p<0.001). From a monthly average of 1223 deliveries pre-Ebola, institutional deliveries also declined during Ebola and then recovered to only 66% of the pre-Ebola level (p<0.001).
CONCLUSIONS
All services assessed were affected by Ebola. Family planning recovered post-Ebola; however, shortfalls were observed in recovery of antenatal care and institutional deliveries. We call for stronger political will, international support and generous funding to change the current state of affairs.
The 2014/2015 Ebola outbreak was the most sustained in history. In Guinea, we compared trends in family planning, antenatal care, and institutional deliveries over the period before, during and after the outbreak.
METHODS
We carried out an ecological study involving all the health facilities during pre-Ebola (1 March 2013 to 28 February 2014), intra-Ebola (1 March 2014 to 28 February 2015) and post-Ebola (1 March to 31 July 2016) periods in Macenta district.
RESULTS
Utilization of family planning declined from a monthly average of 531 visits during the pre-Ebola period to 242 visits in the peak month of the Ebola outbreak (51% decline) but recovered in the post-Ebola period. From a monthly average of 2053 visits pre-Ebola, antenatal care visits declined by 41% during Ebola and then recovered to only 63% of the pre-Ebola level (recovery gap of 37%, p<0.001). From a monthly average of 1223 deliveries pre-Ebola, institutional deliveries also declined during Ebola and then recovered to only 66% of the pre-Ebola level (p<0.001).
CONCLUSIONS
All services assessed were affected by Ebola. Family planning recovered post-Ebola; however, shortfalls were observed in recovery of antenatal care and institutional deliveries. We call for stronger political will, international support and generous funding to change the current state of affairs.