Journal Article > ResearchFull Text
Antimicrob Resist Infect Control. 2023 July 11; Volume 12 (Issue 1); 67.; DOI:10.1186/s13756-023-01271-7
Mambula G, Nanjebe D, Munene A, Guindo O, Salifou A, et al.
Antimicrob Resist Infect Control. 2023 July 11; Volume 12 (Issue 1); 67.; DOI:10.1186/s13756-023-01271-7
BACKGROUND
Antibiotic resistance is a significant public health problem and is responsible for high mortality in children and new-borns. Strengthening the rational use of antibiotics and improving the quality and access to existing antibiotics are important factors in the fight against antibiotic resistance. This study aims to provide knowledge on the use of antibiotics in children in resource-limited countries in order to identify problems and possible avenues for improvement of antibiotics use.
METHODS
We conducted a retrospective study in July 2020 and collected quantitative clinical and therapeutic data on antibiotic prescriptions between January and December 2019 in 4 hospitals or health centres in both Uganda and Niger, respectively from January to December 2019. Semi-structured interviews and focus groups were conducted among healthcare personnel and carers for children under 17 years of age, respectively.
RESULTS
A total of 1,622 children in Uganda and 660 children in Niger (mean age of 3.9 years (SD 4.43)) who received at least one antibiotic were included in the study. In hospital settings, 98.4 to 100% of children prescribed at least one antibiotic received at least one injectable antibiotic. Most hospitalized children received more than one antibiotic in both Uganda (52.1%) and Niger (71.1%). According to the WHO-AWaRe index, the proportion of prescriptions of antibiotics belonging to the Watch category was 21.8% (432/1982) in Uganda and 32.0% (371/1158) in Niger. No antibiotics from the Reserve category were prescribed. Health care provider’s prescribing practices are rarely guided by microbiological analyses. Prescribers are faced with numerous constraints, such as lack of standard national guidelines, unavailability of essential antibiotics at the level of hospital pharmacies, the limited financial means of the families, and pressure to prescribe antibiotics from caregivers as well as from drug company representatives. The quality of some antibiotics provided by the National Medical Stores to the public and private hospitals has been questioned by some health professionals. Self-medication is a widespread practice for the antibiotic treatment of children for economic and access reasons.
CONCLUSION
The study findings indicate that an intersection of policy, institutional norms and practices including individual caregiver or health provider factors, influence antibiotic prescription, administration and dispensing practices.
Antibiotic resistance is a significant public health problem and is responsible for high mortality in children and new-borns. Strengthening the rational use of antibiotics and improving the quality and access to existing antibiotics are important factors in the fight against antibiotic resistance. This study aims to provide knowledge on the use of antibiotics in children in resource-limited countries in order to identify problems and possible avenues for improvement of antibiotics use.
METHODS
We conducted a retrospective study in July 2020 and collected quantitative clinical and therapeutic data on antibiotic prescriptions between January and December 2019 in 4 hospitals or health centres in both Uganda and Niger, respectively from January to December 2019. Semi-structured interviews and focus groups were conducted among healthcare personnel and carers for children under 17 years of age, respectively.
RESULTS
A total of 1,622 children in Uganda and 660 children in Niger (mean age of 3.9 years (SD 4.43)) who received at least one antibiotic were included in the study. In hospital settings, 98.4 to 100% of children prescribed at least one antibiotic received at least one injectable antibiotic. Most hospitalized children received more than one antibiotic in both Uganda (52.1%) and Niger (71.1%). According to the WHO-AWaRe index, the proportion of prescriptions of antibiotics belonging to the Watch category was 21.8% (432/1982) in Uganda and 32.0% (371/1158) in Niger. No antibiotics from the Reserve category were prescribed. Health care provider’s prescribing practices are rarely guided by microbiological analyses. Prescribers are faced with numerous constraints, such as lack of standard national guidelines, unavailability of essential antibiotics at the level of hospital pharmacies, the limited financial means of the families, and pressure to prescribe antibiotics from caregivers as well as from drug company representatives. The quality of some antibiotics provided by the National Medical Stores to the public and private hospitals has been questioned by some health professionals. Self-medication is a widespread practice for the antibiotic treatment of children for economic and access reasons.
CONCLUSION
The study findings indicate that an intersection of policy, institutional norms and practices including individual caregiver or health provider factors, influence antibiotic prescription, administration and dispensing practices.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2018 October 22; Volume 12 (Issue 10); e0006830.; DOI:10.1371/journal.pntd.0006830
Goyal V, Mahajan R, Pandey K, Singh SN, Singh RS, et al.
PLoS Negl Trop Dis. 2018 October 22; Volume 12 (Issue 10); e0006830.; DOI:10.1371/journal.pntd.0006830
BACKGROUND
In 2010, WHO recommended the use of new short-course treatment regimens in kala-azar elimination efforts for the Indian subcontinent. Although phase 3 studies have shown excellent results, there remains a lack of evidence on a wider treatment population and the safety and effectiveness of these regimens under field conditions.
METHODS
This was an open label, prospective, non-randomized, non-comparative, multi-centric trial conducted within public health facilities in two highly endemic districts and a specialist referral centre in Bihar, India. Three treatment regimens were tested: single dose AmBisome (SDA), concomitant miltefosine and paromomycin (Milt+PM), and concomitant AmBisome and miltefosine (AmB+Milt). Patients with complicated disease or significant co-morbidities were treated in the SDA arm. Sample sizes were set at a minimum of 300 per arm, taking into account inter-site variation and an estimated failure risk of 5% with 5% precision. Outcomes of drug effectiveness and safety were measured at 6 months. The trial was prospectively registered with the Clinical Trials Registry India: CTRI/2012/08/002891.
RESULTS
Out of 1,761 patients recruited, 50.6% (n = 891) received SDA, 20.3% (n = 358) AmB+Milt and 29.1% (n = 512) Milt+PM. In the ITT analysis, the final cure rates were SDA 91.4% (95% CI 89.3-93.1), AmB+Milt 88.8% (95% CI 85.1-91.9) and Milt+PM 96.9% (95% CI 95.0-98.2). In the complete case analysis, cure rates were SDA 95.5% (95% CI 93.9-96.8), AmB+Milt 95.5% (95% CI 92.7-97.5) and Milt+PM 99.6% (95% CI 98.6-99.9). All three regimens were safe, with 5 severe adverse events in the SDA arm, two of which were considered to be drug related.
CONCLUSION
All regimens showed acceptable outcomes and safety profiles in a range of patients under field conditions. Phase IV field-based studies, although extremely rare for neglected tropical diseases, are good practice and an important step in validating the results of more restrictive hospital-based studies before widespread implementation, and in this case contributed to national level policy change in India.
In 2010, WHO recommended the use of new short-course treatment regimens in kala-azar elimination efforts for the Indian subcontinent. Although phase 3 studies have shown excellent results, there remains a lack of evidence on a wider treatment population and the safety and effectiveness of these regimens under field conditions.
METHODS
This was an open label, prospective, non-randomized, non-comparative, multi-centric trial conducted within public health facilities in two highly endemic districts and a specialist referral centre in Bihar, India. Three treatment regimens were tested: single dose AmBisome (SDA), concomitant miltefosine and paromomycin (Milt+PM), and concomitant AmBisome and miltefosine (AmB+Milt). Patients with complicated disease or significant co-morbidities were treated in the SDA arm. Sample sizes were set at a minimum of 300 per arm, taking into account inter-site variation and an estimated failure risk of 5% with 5% precision. Outcomes of drug effectiveness and safety were measured at 6 months. The trial was prospectively registered with the Clinical Trials Registry India: CTRI/2012/08/002891.
RESULTS
Out of 1,761 patients recruited, 50.6% (n = 891) received SDA, 20.3% (n = 358) AmB+Milt and 29.1% (n = 512) Milt+PM. In the ITT analysis, the final cure rates were SDA 91.4% (95% CI 89.3-93.1), AmB+Milt 88.8% (95% CI 85.1-91.9) and Milt+PM 96.9% (95% CI 95.0-98.2). In the complete case analysis, cure rates were SDA 95.5% (95% CI 93.9-96.8), AmB+Milt 95.5% (95% CI 92.7-97.5) and Milt+PM 99.6% (95% CI 98.6-99.9). All three regimens were safe, with 5 severe adverse events in the SDA arm, two of which were considered to be drug related.
CONCLUSION
All regimens showed acceptable outcomes and safety profiles in a range of patients under field conditions. Phase IV field-based studies, although extremely rare for neglected tropical diseases, are good practice and an important step in validating the results of more restrictive hospital-based studies before widespread implementation, and in this case contributed to national level policy change in India.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2016 September 14; Volume 10 (Issue 9); DOI:10.1371/journal.pntd.0004880
Wassuna M, Njenga SN, Balasegaram M, Alexander N, Omollo R, et al.
PLoS Negl Trop Dis. 2016 September 14; Volume 10 (Issue 9); DOI:10.1371/journal.pntd.0004880
SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2019 January 17; Volume 13 (Issue 1); DOI:10.1371/journal.pntd.0006988
Diro EGJ, Blesson S, Edwards T, Koert R, Ritmeijer KKD, et al.
PLoS Negl Trop Dis. 2019 January 17; Volume 13 (Issue 1); DOI:10.1371/journal.pntd.0006988
BACKGROUND
Visceral leishmaniasis (VL) in human immunodeficiency virus (HIV) co-infected patients requires special case management. AmBisome monotherapy at 40 mg/kg is recommended by the World Health Organization. The objective of the study was to assess if a combination of a lower dose of AmBisome with miltefosine would show acceptable efficacy at the end of treatment.
METHODOLOGY/PRINCIPAL FINDINGS
An open-label, non-comparative randomized trial of AmBisome (30 mg/kg) with miltefosine (100 mg/day for 28 days), and AmBisome monotherapy (40 mg/kg) was conducted in Ethiopian VL patients co-infected with HIV (NCT02011958). A sequential design was used with a triangular continuation region. The primary outcome was parasite clearance at day 29, after the first round of treatment. Patients with clinical improvement but without parasite clearance at day 29 received a second round of the allocated treatment. Efficacy was evaluated again at day 58, after completion of treatment.
Recruitment was stopped after inclusion of 19 and 39 patients in monotherapy and combination arms respectively, as per pre-specified stopping rules. At D29, intention-to-treat efficacy in the AmBisome arm was 70% (95% CI 45–87%) in the unadjusted analysis, and 50% (95% CI 27–73%) in the adjusted analysis, while in the combination arm, it was 81% (95% CI 67–90%) and 67% (95% CI 48–82%) respectively. At D58, the adjusted efficacy was 55% (95% CI 32–78%) in the monotherapy arm, and 88% (95% CI 79–98%) in the combination arm.
No major safety concerns related to the study medication were identified. Ten SAEs were observed within the treatment period, and 4 deaths unrelated to the study medication.
CONCLUSIONS/SIGNIFICANCE
The extended treatment strategy with the combination regimen showed the highest documented efficacy in HIV-VL patients; these results support a recommendation of this regimen as first-line treatment strategy for HIV-VL patients in eastern Africa.
TRIAL REGISTRATION NUMBER
www.clinicaltrials.gov NCT02011958
Visceral leishmaniasis (VL) in human immunodeficiency virus (HIV) co-infected patients requires special case management. AmBisome monotherapy at 40 mg/kg is recommended by the World Health Organization. The objective of the study was to assess if a combination of a lower dose of AmBisome with miltefosine would show acceptable efficacy at the end of treatment.
METHODOLOGY/PRINCIPAL FINDINGS
An open-label, non-comparative randomized trial of AmBisome (30 mg/kg) with miltefosine (100 mg/day for 28 days), and AmBisome monotherapy (40 mg/kg) was conducted in Ethiopian VL patients co-infected with HIV (NCT02011958). A sequential design was used with a triangular continuation region. The primary outcome was parasite clearance at day 29, after the first round of treatment. Patients with clinical improvement but without parasite clearance at day 29 received a second round of the allocated treatment. Efficacy was evaluated again at day 58, after completion of treatment.
Recruitment was stopped after inclusion of 19 and 39 patients in monotherapy and combination arms respectively, as per pre-specified stopping rules. At D29, intention-to-treat efficacy in the AmBisome arm was 70% (95% CI 45–87%) in the unadjusted analysis, and 50% (95% CI 27–73%) in the adjusted analysis, while in the combination arm, it was 81% (95% CI 67–90%) and 67% (95% CI 48–82%) respectively. At D58, the adjusted efficacy was 55% (95% CI 32–78%) in the monotherapy arm, and 88% (95% CI 79–98%) in the combination arm.
No major safety concerns related to the study medication were identified. Ten SAEs were observed within the treatment period, and 4 deaths unrelated to the study medication.
CONCLUSIONS/SIGNIFICANCE
The extended treatment strategy with the combination regimen showed the highest documented efficacy in HIV-VL patients; these results support a recommendation of this regimen as first-line treatment strategy for HIV-VL patients in eastern Africa.
TRIAL REGISTRATION NUMBER
www.clinicaltrials.gov NCT02011958
Protocol > Research Protocol
Hailu ADE, Diro EGJ, Kolja S, Ritmeijer KKD, Yifru S, et al.
2018 July 1
General Objectives
The overall objective of this trial is to identify a safe and effective treatment for VL in HIV coinfected
patients.
Primary Objective:
To evaluate at day 29 assessment the efficacy of a combination regimen of AmBisome®
+
miltefosine and AmBisome®
monotherapy in Ethiopian co-infected HIV + VL patients.
Secondary Objectives:
1. To evaluate relapse-free survival at day 390 (after initial cure at day 29 or cure at day 58 after
extended treatment).
2. To assess safety of the regimens.
Other objectives:
1.To evaluate of viral load and CD4 count in all patients
2. To evaluate the pharmacokinetics of ARV, Ambisome and miltefosine and immune function
markers in a subset of patients
The overall objective of this trial is to identify a safe and effective treatment for VL in HIV coinfected
patients.
Primary Objective:
To evaluate at day 29 assessment the efficacy of a combination regimen of AmBisome®
+
miltefosine and AmBisome®
monotherapy in Ethiopian co-infected HIV + VL patients.
Secondary Objectives:
1. To evaluate relapse-free survival at day 390 (after initial cure at day 29 or cure at day 58 after
extended treatment).
2. To assess safety of the regimens.
Other objectives:
1.To evaluate of viral load and CD4 count in all patients
2. To evaluate the pharmacokinetics of ARV, Ambisome and miltefosine and immune function
markers in a subset of patients
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2010 October 26; Volume 4 (Issue 10); DOI:10.1371/journal.pntd.0000709
Hailu ADE, Musa AM, Wasunna M, Balasegaram M, Yifru S, et al.
PLoS Negl Trop Dis. 2010 October 26; Volume 4 (Issue 10); DOI:10.1371/journal.pntd.0000709
Visceral leishmaniasis (VL) is a major health problem in developing countries. The untreated disease is fatal, available treatment is expensive and often toxic, and drug resistance is increasing. Improved treatment options are needed. Paromomycin was shown to be an efficacious first-line treatment with low toxicity in India.
Journal Article > ResearchFull Text
Clin Drug Investig. 2017 March 1; Volume 37 (Issue 3); 259-272.; DOI:10.1007/s40261-016-0481-0
Kimutai R, Musa AM, Njoroge SM, Omollo R, Alves F, et al.
Clin Drug Investig. 2017 March 1; Volume 37 (Issue 3); 259-272.; DOI:10.1007/s40261-016-0481-0
INTRODUCTION
In 2010, WHO recommended a new first-line treatment for visceral leishmaniasis (VL) in Eastern Africa. The new treatment, a combination of intravenous (IV) or intramuscular (IM) sodium stibogluconate (SSG) and IM paromomycin (PM) was an improvement over SSG monotherapy, the previous first-line VL treatment in the region. To monitor the new treatment's safety and effectiveness in routine clinical practice a pharmacovigilance (PV) programme was developed.
METHODS
A prospective PV cohort was developed. Regulatory approval was obtained in Sudan, Kenya, Uganda and Ethiopia. Twelve sentinel sites sponsored by the Ministries of Health, Médecins Sans Frontières (MSF) and Drugs for Neglected Diseases initiative (DNDi) participated. VL patients treated using the new treatment were consented and included in a common registry that collected demographics, baseline clinical characteristics, adverse events, serious adverse events and treatment outcomes. Six-monthly periodic safety update reports (PSUR) were prepared and reviewed by a PV steering committee.
RESULTS
Overall 3126 patients were enrolled: 1962 (62.7%) from Sudan, 652 (20.9%) from Kenya, 322 (10.3%) from Ethiopia and 190 (6.1%) from Uganda. Patients were mostly male children (68.1%, median age 11 years) with primary VL (97.8%). SSG-PM initial cure rate was 95.1%; no geographical differences were noted. HIV/VL co-infected patients and patients older than 50 years had initial cure rates of 56 and 81.4%, respectively, while 1063 (34%) patients had at least one adverse event (AE) during treatment and 1.92% (n = 60) had a serious adverse event (SAE) with a mortality of 1.0% (n = 32). There were no serious unexpected adverse drug reactions.
CONCLUSIONS
This first regional PV programme in VL supports SSG-PM combination as first-line treatment for primary VL in Eastern Africa. SSG-PM was effective and safe except in HIV/VL co-infected or older patients. Active PV surveillance of targeted safety, effectiveness and key VL outcomes such us VL relapse, PKDL and HIV/VL co-infection should continue and PV data integrated to national and WHO PV databases.
In 2010, WHO recommended a new first-line treatment for visceral leishmaniasis (VL) in Eastern Africa. The new treatment, a combination of intravenous (IV) or intramuscular (IM) sodium stibogluconate (SSG) and IM paromomycin (PM) was an improvement over SSG monotherapy, the previous first-line VL treatment in the region. To monitor the new treatment's safety and effectiveness in routine clinical practice a pharmacovigilance (PV) programme was developed.
METHODS
A prospective PV cohort was developed. Regulatory approval was obtained in Sudan, Kenya, Uganda and Ethiopia. Twelve sentinel sites sponsored by the Ministries of Health, Médecins Sans Frontières (MSF) and Drugs for Neglected Diseases initiative (DNDi) participated. VL patients treated using the new treatment were consented and included in a common registry that collected demographics, baseline clinical characteristics, adverse events, serious adverse events and treatment outcomes. Six-monthly periodic safety update reports (PSUR) were prepared and reviewed by a PV steering committee.
RESULTS
Overall 3126 patients were enrolled: 1962 (62.7%) from Sudan, 652 (20.9%) from Kenya, 322 (10.3%) from Ethiopia and 190 (6.1%) from Uganda. Patients were mostly male children (68.1%, median age 11 years) with primary VL (97.8%). SSG-PM initial cure rate was 95.1%; no geographical differences were noted. HIV/VL co-infected patients and patients older than 50 years had initial cure rates of 56 and 81.4%, respectively, while 1063 (34%) patients had at least one adverse event (AE) during treatment and 1.92% (n = 60) had a serious adverse event (SAE) with a mortality of 1.0% (n = 32). There were no serious unexpected adverse drug reactions.
CONCLUSIONS
This first regional PV programme in VL supports SSG-PM combination as first-line treatment for primary VL in Eastern Africa. SSG-PM was effective and safe except in HIV/VL co-infected or older patients. Active PV surveillance of targeted safety, effectiveness and key VL outcomes such us VL relapse, PKDL and HIV/VL co-infection should continue and PV data integrated to national and WHO PV databases.