James H Stark Eve Wool Lena Tran Elizabeth Robinson Meaghan Chemelski Daniel Weibel Wan-Ting Huang Sonali Kochhar Janet R Hardy Steven Bailey Edward Galiwango Dan Kajungu

International Health

Background

Standardized case definitions for obstetric and neonatal outcomes were developed by the Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project. These definitions can facilitate comparable assessment of maternal immunization safety surveillance and research. This study assessed the capabilities of health centers (HC) in Uganda to implement these definitions in a low-income country, which has not been explored.

Methods

Healthcare practitioners at 15 government-accredited health centers and one government-funded district hospital in the Iganga-Mayuge Health and Demographic Surveillance Site (IMHDSS) in Uganda were interviewed about the facility’s clinical diagnostic and laboratory capabilities. Five obstetric and five neonatal case definitions were evaluated. Definitions with the highest diagnostic certainty were designated as level 1, while definitions that decreased in certainty were designated as level 2 or 4. HCs were evaluated on diagnostic and laboratory capabilities to apply the GAIA definitions.

Results

Higher-level facilities in the IMHDSS demonstrated the ability to diagnose more specific levels of the GAIA obstetric and neonatal outcomes than lower-level facilities. Furthermore, for the neonatal outcome assessment, there was an increased ability to diagnose outcomes moving from GAIA level 1 to level 3.

Conclusions

The ability of health centers to implement globally standardized definitions is promising for implementation of standardized data collection methods for global vaccine safety surveillance and research.

2018-09-25

Dan Kajungu Erhart Annette Talisuna Ambrose O Bassat Q Karema C Nabasumba C Nambozi M Tinto H Kremsner P Meremikwu M D’Alessandro U Speybroeck N

PLOSE ONE

BACKGROUND:

Pharmacovigilance programmes monitor and help to ensure the safe use of medicines which is critical to the success of public health programmes. The commonest method used for discovering previously unknown safety risks is spontaneous notifications. In this study, we examine the use of data mining algorithms to identify signals from adverse events reported in a phase IIIb/IV clinical trial evaluating the efficacy and safety of several Artemisinin-based combination therapies (ACTs) for treatment of uncomplicated malaria in African children.

METHODS:

We used paediatric safety data from a multi-site, multi-country clinical study conducted in seven African countries (Burkina Faso, Gabon, Nigeria, Rwanda, Uganda, Zambia, and Mozambique). Each site compared three out of four ACTs, namely amodiaquine-artesunate (ASAQ), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL) or chlorproguanil/dapsone and artesunate (CD+A). We examine two pharmacovigilance signal detection methods, namely proportional reporting ratio and Bayesian Confidence Propagation Neural Network on the clinical safety dataset.

RESULTS:

Among the 4,116 children (6-59 months old) enrolled and followed up for 28 days post-treatment, a total of 6,238 adverse events were reported resulting into 346 drug-event combinations. Nine signals were generated both by proportional reporting ratio and Bayesian Confidence Propagation Neural Network. A review of the manufacturer package leaflets, an online Multi-Drug Symptom/Interaction Checker (DoubleCheckMD) and further by therapeutic area experts reduced the number of signals to five. The ranking of some drug-adverse reaction pairs on the basis of their signal index differed between the two methods.

CONCLUSIONS:

Our two data mining methods were equally able to generate suspected signals using the pooled safety data from a phase IIIb/IV clinical trial. This analysis demonstrated the possibility of utilising clinical studies safety data for key pharmacovigilance activities like signal detection and evaluation. This approach can be applied to complement the spontaneous reporting systems which are limited by underreporting.

2014-05-20

Christian Rassi Dan Kajungu Sandrine Martin Jorge Arroz Jamie Tallant Celine Zegers de Beyl Helen Counihan James N. Newell Anna Phillips Jane Whitton Artur Manuel Muloliwa Kirstie Graham

PLoS Neglected Tropical Diseases

BACKGROUND:

Schistosomiasis is a parasitic disease which affects almost 300 million people worldwide each year. It is highly endemic in Mozambique. Prevention and control of schistosomiasis relies mainly on mass drug administration (MDA), as well as adoption of basic sanitation practices. Individual and community perceptions of schistosomiasis are likely to have a significant effect on prevention and control efforts. In order to establish a baseline to evaluate a community engagement intervention with a focus on schistosomiasis, a survey to determine knowledge, attitudes and practices relating to the disease was conducted.

METHODOLOGY/PRINCIPAL FINDINGS:

A representative cross-sectional household survey was carried out in four districts of Nampulaprovince, Mozambique. Interviews were conducted in a total of 791 households, using a structured questionnaire. While awareness of schistosomiasis was high (91%), correct knowledge of how it is acquired (18%), transmitted (26%) and prevented (13%) was low among those who had heard of the disease. Misconceptions, such as the belief that schistosomiasis is transmitted through sexual contact (27%), were common. Only about a third of those who were aware of the disease stated that they practiced a protective behaviour and only a minority of those (39%) reported an effective behaviour. Despite several rounds of MDA for schistosomiasis in the recent past, only a small minority of households with children reported that at least one of them had received a drug to treat the disease (9%).

CONCLUSION/SIGNIFICANCE:

Poor knowledge of the causes of schistosomiasis and how to prevent it, coupled with persisting misconceptions, continue to pose barriers to effective disease prevention and control. To achieve high levels of uptake of MDA and adoption of protective behaviours, it will be essential to engage individuals and communities, improving their understanding of the causes and symptoms of schistosomiasis, recommended prevention mechanisms and the rationale behind MDA.

2016-03-04

Helen Byomire N Victoria Nambasa Leonard Manirakiza Donna Kusemererwa Dan Kajungu Sten Olsson Niko Speybroeck

Drug Safety

INTRODUCTION:

Uganda has rapidly increased access to antimalarial medicines in an effort to address the huge malaria disease burden. Pharmacovigilance information is important to guide policy decisions.

OBJECTIVES:

The purpose of this study was to establish the burden of adverse drug reactions (ADRs) and associated risk factors for developing ADRs to artemisinin-based antimalarial treatment in Uganda.

METHODS:

An active follow-up study was conducted between April and July 2017 in a cohort of patients receiving treatment for uncomplicated malaria in the Iganga, Mayuge, and Kampala districts.

RESULTS:

A total of 782 patients with a median age of 22 years (58.6% females) were recruited into this study, with the majority recruited from public health facilities (97%). Diagnostic tests before treatment were performed for 76% of patients, and 97% of patients received artemether/lumefantrine. The prevalence of ADRs was 22.5% (176/782); however, the total number of ADRs was 245 since some patients reported more than one ADR. The most commonly reported reactions were general body weakness (24%), headache (13%), and dizziness (11%). Women were more likely to develop an ADR (adjusted odds ratio [aOR] 1.8, 95% confidence interval [CI] 1.1-2.9), urban dwellers were more likely to develop an ADR than rural residents (aOR 9.9, 95% CI 5.4-17.9), and patients with comorbidities were more likely to develop an ADR than those without (aOR 7.4, 95% CI 4.4-12.3).

CONCLUSION:

The burden of ADRs is high among women and in patients from urban settings and those with comorbidities. Such risk factors need to be considered in order to optimise therapy. Close monitoring of ADRs is key in implementation of the malaria treatment policy.

2018-08-22

Helen Ndagije Victoria Nambasa, Elizabeth Namagala Huldah Nassali Dan Kajungu Gordon Sematiko Sten Olsson Shanthi Pal

Drug Safety

BACKGROUND:

Although the national HIV control programme in Uganda has a well-established system for monitoring disease progression and treatment outcomes, monitoring of adverse drug reactions (ADRs) is inadequate. In order to address under-reporting of ADRs, the National Pharmacovigilance Centre, in collaboration with the HIV control programme, piloted a targeted spontaneous reporting (TSR) system as a complementary method to traditional spontaneous reporting.

METHODS:

From April 2012 to March 2014, all cases of suspected renal toxicity in 10,225 patients on tenofovir-based regimens were monitored in the regional pharmacovigilance centres of Masaka and Mbale. The identification of renal toxicity was performed using serum creatinine, urinalysis, and other signs and symptoms of kidney injury.

RESULTS:

There was one suspected renal toxicity reported for every 200 patients on a tenofovir-based regimen. Some of the serious reactions reported were death in two cases and bone demineralisation in five patients. Most of patients had been on treatment for 2 years. Those that had been on tenofovir for more than 4 years had raised serum creatinine levels, emphasising the importance of monitoring for the risk of renal damage for longer. We also found that the reporting rate of suspected ADRs for all medicines in the two sites increased almost fivefold during the implementation period.

CONCLUSION:

Although the occurrence of suspected tenofovir renal toxicity of HIV patients is low, there is need to monitor those at risk so as to prevent irreversible kidney injury. TSR can complement spontaneous reporting for collecting safety data on particular drugs and increase ADR reporting rates.

2015-04-21

Hilda Ampadu Alexander N. O. Dodoo Samuel Bosomprah Samantha Akakpo Pierre Hugo Helga Gardarsdottir H. G. M. Leufkens Dan Kajungu Kwaku Poku Asante

Drug Safety

INTRODUCTION:

Injectable artesunate (Inj AS) is the World Health Organization (WHO)-recommended product for treating severe malaria. However, despite widespread usage, there are few published safety studies involving large populations in real-world settings. In this study, we sought to assess the incidence of common adverse events (AEs) following the intake of Inj AS in real-life settings.

METHODS:

This is a modified cohort event monitoring study involving patients who were administered with Inj AS at eight sites (four each in Ghana and Uganda) between May and December 2016. Patients were eligible for inclusion if they had severe/complicated malaria and were able and willing to participate in the study. Eligible patients were followed up by telephone or hospital or home visit on Days 7, 14, 21 and 28 after drug administration to document AEs and serious AEs (SAEs). Patients were also encouraged to report all AEs at any time during the study period. The Kaplan-Meier method was used to estimate the proportion of patients with any AEs by end of Day 28. Causality assessment was made on all AEs/SAEs using the WHO/UMC (Uppsala Monitoring Centre) causality method.

RESULTS:

A total of 1103 eligible patients were administered Inj AS, of which 360 patients were in Ghana and 743 in Uganda. The incidence of any AE by the end of follow-up among patients treated with AS was estimated to be 17.9% (197/1103) (95% confidence interval [CI] 15.8-20.3). The median time-to-onset of any AEs was 9 days (interquartile range (IQR) = 4, 14). The top five AEs recorded among patients treated with AS were pyrexia (3.5%), abdominal pain (2.5%), diarrhoea (1.7%), cough (1.5%) and asthenia (1.5%). Most of these top five AEs occurred in the first 14 days following treatment. Regarding the relatedness of these AEs to Inj AS, 78.9% of pyrexia (30/38), 63.0% of pain (17/27), 68.4% of diarrhoea (13/19), 85.5% of cough (14/16) and 75.0% of asthenia (12/16) were assessed as 'possibly' related. There were 17 SAEs including 13 deaths. Two of the deaths are 'possibly' related to Inj AS, as were three non-fatal SAEs: severe abdominal pain, failure of therapy and severe anaemia.

CONCLUSION:

The incidence of common AEs among patients treated with Inj AS in real-world settings was found to be relatively low. Future studies should consider larger cohorts to document rare AEs as well.

2018-04-20

Angela Baschieri, Vladimir S Gordeev, Joseph Akuze, Doris Kwesiga, Hannah Blencowe, Simon Cousens, Peter Waiswa, Ane B Fisker, Sanne M Thysen, Amabelia Rodrigues, Gashaw A Biks, Solomon M Abebe, Kassahun A Gelaye, Mezgebu Y Mengistu, Bisrat M Geremew, Tadesse G Delele, Adane K Tesega, Temesgen A Yitayew, Simon Kasasa, Edward Galiwango, Davis Natukwatsa, Dan Kajungu, Yeetey AK Enuameh, Obed E Nettey, Francis Dzabeng, Seeba Amenga-Etego, Sam K Newton, Alexander A Manu, Charlotte Tawiah, Kwaku P Asante, Seth Owusu-Agyei, Nurul Alam, M M Haider, Sayed S Alam, Fred Arnold, Peter Byass, Trevor N Croft, Kobus Herbst, Sunita Kishor, Florina Serbanescu, and Joy E Lawn

Journal of Global Health

Background

Under-five and maternal mortality were halved in the Millennium Development Goals (MDG) era, with slower reductions for 2.6 million neonatal deaths and 2.6 million stillbirths. The Every Newborn Action Plan aims to accelerate progress towards national targets, and includes an ambitious Measurement Improvement Roadmap. Population-based household surveys, notably Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys, are major sources of population-level data on child mortality in countries with weaker civil registration and vital statistics systems, where over two-thirds of global child deaths occur. To estimate neonatal/child mortality and pregnancy outcomes (stillbirths, miscarriages, birthweight, gestational age) the most common direct methods are: (1) the standard DHS-7 with Full Birth History with additional questions on pregnancy losses in the past 5 years (FBH+ ) or (2) a Full Pregnancy History (FPH). No direct comparison of these two methods has been undertaken, although descriptive analyses suggest that the FBH+ may underestimate mortality rates particularly for stillbirths.

Methods

This is the protocol paper for the Every Newborn-INDEPTH study (INDEPTH Network, International Network for the Demographic Evaluation of Populations and their Health Every Newborn, Every Newborn Action Plan), aiming to undertake a randomised comparison of FBH+ and FPH to measure pregnancy outcomes in a household survey in five selected INDEPTH Network sites in Africa and South Asia (Bandim in urban and rural Guinea-Bissau; Dabat in Ethiopia; Iganga Mayuge in Uganda; Kintampo in Ghana; Matlab in Bangladesh). The survey will reach >68000 pregnancies to assess if there is ≥15% difference in stillbirth rates. Additional questions will capture birthweight, gestational age, birth/death certification, termination of pregnancy and fertility intentions. The World Bank’s Survey Solutions platform will be tailored for data collection, including recording paradata to evaluate timing. A mixed methods assessment of barriers and enablers to reporting of pregnancy and adverse pregnancy outcomes will be undertaken.

Conclusions

This large-scale study is the first randomised comparison of these two methods to capture pregnancy outcomes. Results are expected to inform the evidence base for survey methodology, especially in DHS, regarding capture of stillbirths and other outcomes, notably neonatal deaths, abortions (spontaneous and induced), birthweight and gestational age. In addition, this study will inform strategies to improve health and demographic surveillance capture of neonatal/child mortality and pregnancy outcomes.

2019-06-14

H. Hilda Ampadu Kwaku Poku Asante Samuel Bosomprah Samantha Akakpo Pierre Hugo Helga Gardarsdottir Hubert G. M. Leufkens Dan Kajungu Alexander N. O. Dodoo

Malaria Journal

Background:

Injectable artesunate (AS) is the World Health Organization (WHO) recommended medication for the treatment of severe malaria followed with an oral artemisinin-based combination therapy (ACT). There are few studies indicating how physicians prescribe injectable AS, injectable quinine (Q) or injectable artemether (AR) and ACT for severe malaria. This study was undertaken to evaluate prescription compliance to the WHO recommendation in 8 public health facilities in Ghana and Uganda. This was a modified cohort event monitoring study involving patients who were administered with injectable anti-malarial for treatment of presumed or confirmed severe malaria. Patients prescribed at least one dose of injectable artesunate, artemether or quinine qualified to enrol in the study. Patients were recruited at inpatient facilities and followed up in the hospital, by phone or at home. Following WHO recommendations, patients are to be prescribed 3 doses of injectable AS, Q or AR for at least 24 h followed with oral ACT. Compliance rate was estimated as the number of patient prescriptions that met the WHO recommendation for treatment of severe malaria divided by the total number of patients who completed the study by end of follow up. Log-binomial regression model was used to identify predictors for compliance. Based on the literature and limitations of available data from the patients’ record, the diagnosis results, age, gender, weight, and country were considered as potential predictors of prescriber adherence to the WHO recommendations.

Results

A total of 1191 patients completed the study, of which 93% were prescribed injectable AS, 3.1% (injectable AR or Q) with 32.5% prescribed follow-on oral ACT and 26% on concomitant antibiotics. 391 (32.8%) were in Ghana and 800 (67.2%) in Uganda. There were 582 (48.9%) women. The median age was 3.9 years (IQR = 2, 9) and median weight was 13 kg (IQR = 10, 20). Of the 1191 patients, 329 of the prescriptions complied with the WHO recommendation (compliance rate = 27.6%; 95% CI = [25.2, 30.2]). Diagnostic results (Adjusted prevalence ratio (aPR) = 4.56; 95% = [3.42, 6.08]; p < 0.0001) and weight (20 + kg vs < 10 kg: aPR = 0.65; 95% = [0.44, 0.96]; p = 0.015) were identified as factors independently associated with compliance.

Conclusion

Injectable AS is the most commonly prescribed medicine in the management of severe malaria in Ghana and Uganda. However, adherence to the WHO recommendation of at least 3 doses of injectable anti-malarial in 24 h followed by a full course of ACT is low, at less than 30%.

2019-02-04