Browsing by Author "Ssenkusu, John M."

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    Acute Kidney Injury In Ugandan Children With Severe Malaria Is Associated With Long-Term Behavioral Problems
    (PloS one, 2019) Hickson, Meredith R.; Conroy, Andrea L.; Bangirana, Paul; Opoka, Robert O.; Idro, Richard; Ssenkusu, John M.; John, Chandy C.
    Acute kidney injury (AKI) is a risk factor for neurocognitive impairment in severe malaria (SM), but the impact of AKI on long-term behavioral outcomes following SM is unknown.We conducted a prospective study on behavioral outcomes of Ugandan children 1.5 to 12 years of age with two forms of severe malaria, cerebral malaria (CM, n = 226) or severe malarial anemia (SMA, n = 214), and healthy community children (CC, n = 173). AKI was defined as a 50% increase in creatinine from estimated baseline. Behavior and executive function were assessed at baseline and 6, 12, and 24 months later using the Child Behavior Checklist and Behavior Rating Inventory of Executive Function, respectively. Age-adjusted z-scores were computed for each domain based on CC scores. The association between AKI and behavioral outcomes was evaluated across all time points using linear mixed effect models, adjusting for sociodemographic variables and disease severity.AKI was present in 33.2% of children with CM or SMA at baseline. Children ≥6 years of age with CM or SMA who had AKI on admission had worse scores in socio-emotional function in externalizing behaviors (Beta (95% CI), 0.52 (0.20, 0.85), p = 0.001), global executive function (0.48 (0.15, 0.82), p = 0.005) and behavioral regulation (0.66 (0.32, 1.01), p = 0.0002) than children without AKI. There were no behavioral differences associated with AKI in children <6 years of age.AKI is associated with long-term behavioral problems in children ≥6 years of age with CM or SMA, irrespective of age at study enrollment.
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    Acute Kidney Injury Is Associated With Impaired Cognition And Chronic Kidney Disease In A Prospective Cohort Of Children With Severe Malaria
    (BMC medicine, 2019) Conroy, Andrea L.; Opoka, Robert O.; Bangirana, Paul; Idro, Richard; Ssenkusu, John M.; Datta, Dibyadyuti; Hodges, James S.; Morgan, Catherine; John, Chandy C.
    Acute kidney injury (AKI) is a recognized complication of pediatric severe malaria, but its long-term consequences are unknown. Ugandan children with cerebral malaria (CM, n = 260) and severe malaria anemia (SMA, n = 219) or community children (CC, n = 173) between 1.5 and 12 years of age were enrolled in a prospective cohort study. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to retrospectively define AKI and chronic kidney disease (CKD). Cognitive testing was conducted using the Mullen Scales of Early Learning in children < 5 and Kaufman Assessment Battery for Children (K-ABC) second edition in children ≥ 5 years of age.The prevalence of AKI was 35.1%, ranging from 25.1% in SMA to 43.5% in CM. In-hospital mortality was 11.9% in AKI compared to 4.2% in children without AKI (p = 0.001), and post-discharge mortality was 4.7% in AKI compared to 1.3% in children without AKI (p = 0.030) corresponding to an all-cause adjusted hazard ratio of 2.30 (95% CI 1.21, 4.35). AKI was a risk factor for short- and long-term neurocognitive impairment. At 1 week post-discharge, the frequency of neurocognitive impairment was 37.3% in AKI compared to 13.5% in children without AKI (adjusted odds ratio (aOR) 2.31 [95% CI 1.32, 4.04]); at 1-year follow-up, it was 13.3% in AKI compared to 3.4% in children without AKI (aOR 2.48 [95% CI 1.01, 6.10]), and at 2-year follow-up, it was 13.0% in AKI compared to 3.4% in children without AKI (aOR 3.03 [95% CI 1.22, 7.58]). AKI was a risk factor for CKD at 1-year follow-up: 7.6% of children with severe malaria-associated AKI had CKD at follow-up compared to 2.8% of children without AKI (p = 0.038) corresponding to an OR of 2.81 (95% CI 1.02, 7.73). The presenting etiology of AKI was consistent with prerenal azotemia, and lactate dehydrogenase as a marker of intravascular hemolysis was an independent risk factor for AKI in CM and SMA (p < 0.0001). In CM, AKI was associated with the presence and severity of retinopathy (p < 0.05) and increased cerebrospinal fluid albumin suggestive of blood-brain barrier disruption.AKI is a risk factor for long-term neurocognitive impairment and CKD in pediatric severe malaria.
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    Adherence to Antiepileptic Drugs among Children Attending a Tertiary Health Unit in a Low Resource Setting.
    (Pan African Medical Journal, 2014) Nazziwa, Rose; Mwesige, Angelina Kakooza; Obua, Celestino; Ssenkusu, John M.; Mworozi, Edison
    Epilepsy is one of the neglected and highly stigmatised diseases, yet it is very common affecting about 70 million people worldwide. In Uganda, the estimated prevalence of epilepsy is 13% with about 156 new cases per 100,000 people per year. Adherence to antiepileptic drugs is crucial in achieving seizure control yet in Uganda; there is lack of information on adherence to antiepileptic drugs and the factors that affect this among children. This study was therefore designed to determine the level of adherence to antiepileptic drugs and the factors that are associated with non adherence. Methods: In a cross sectional study, 122 children who met the inclusion criteria were enrolled and interviewed using a pretested questionnaire. Assessment of adherence to antiepileptic drugs was done by self report and assay of serum drug levels of the antiepileptic drugs. Focus group discussions were held to further evaluate the factors that affect adherence. Results: Age range was 6 months - 16 years, male to female ratio 1.3:1 and majority had generalised seizures 76 (62.3%). Adherence to antiepileptic drugs by self report was 79.5% and 22.1% by drug levels. Majority of the children in both adherent and non adherent groups by self report had inadequate drug doses (95/122).Children were found to be more non-adherent if the caregiver had an occupation (p-value 0.030, 95%CI 1.18-28.78) Majority of children had good adherence levels when estimated by self report. The caregiver having an occupation was found to increase the likelihood of non adherence in a child.
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    Alcohol use and associated factors among adolescent boys and young men in Kampala, Uganda
    (Substance Abuse Treatment, Prevention, and Policy, 2021) Ndugwa Kabwama, Steven; Matovu, Joseph K.B.; Ssenkusu, John M.; Ssekamatte, Tonny; Wanyenze, Rhoda K.
    Alcohol use leads to about 3 million deaths globally. The alcohol industry employs marketing strategies to establish their brands in the lives of young people at a time when addictive behaviors are initiated and reinforced. We conducted a survey among adolescent boys and young men (ABYM) to estimate the prevalence of alcohol use and associated factors using the Health Belief Model as the guiding framework. The study was conducted among ABYM in- or out-of-school aged 10–24 years in Kampala, Uganda. We used questions adopted from the Global School-based Student Health Survey and the WHO STEPwise approach to Surveillance questionnaire to collect data. The outcome of interest was alcohol use within 30 days before the interview. We also asked about characteristics such as alcohol use by siblings, parents/ guardians, school status among others. We used odds ratios obtained via a logistic regression model as the measure of association. A total of 2500 ABYM participated, of which 262 (10.5 %, 95 %CI 9.3–11.7) had consumed alcohol within 30 days before the interview. Out-of-school ABYM had higher odds of consuming alcohol compared with their inschool counterparts AOR 1.55 (95 %CI 1.09–2.20). Compared with ABYM whose parents/ guardians did not drink alcohol, ABYM whose both parents consumed alcohol had higher odds of consuming alcohol AOR 2.24 (95 %CI 1.38–3.64) as were those with only a mother or female guardian who consumed alcohol AOR 1.95 (95 %CI 1.11–3.41). ABYM with siblings that drink alcohol had higher odds of consuming alcohol AOR 2.25 (95 %CI 1.80–3.52). ABYM who possessed items with an alcohol brand logo had higher odds of consuming alcohol AOR 2.00 (95 %CI 1.33–3.01).
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    Delayed Iron Does Not Alter Cognition Or Behavior Among Children With Severe Malaria And Iron Deficiency
    (Pediatric research, 2020) Ssemata, Andrew S.; Hickson, Meredith; Ssenkusu, John M.; Cusick, Sarah E.; Nakasujja, Noeline; Opoka, Robert O.; Kroupina, Maria; Georgieff, Michael K.; Bangirana, Paul; John, Chandy C.
    Malaria and iron deficiency (ID) in childhood are both associated with cognitive and behavioral dysfunction. The current standard of care for children with malaria and ID is concurrent antimalarial and iron therapy. Delaying iron therapy until inflammation subsides could increase iron absorption but also impair cognition.In this study, Ugandan children 18 months to 5 years old with cerebral malaria (CM, n = 79), severe malarial anemia (SMA, n = 77), or community children (CC, n = 83) were enrolled and tested for ID. Children with ID were randomized to immediate vs. 28-day delayed iron therapy. Cognitive and neurobehavioral outcomes were assessed at baseline and 6 and 12 months (primary endpoint) after enrollment.All children with CM or SMA and 35 CC had ID (zinc protoporphyrin concentration ≥80 μmol/mol heme). No significant differences were seen at 12-month follow-up in overall cognitive ability, attention, associative memory, or behavioral outcomes between immediate and delayed iron treatment (mean difference (standard error of mean) ranged from −0.2 (0.39) to 0.98 (0.5), all P ≥ 0.06).Children with CM or SMA and ID who received immediate vs. delayed iron therapy had similar cognitive and neurobehavioral outcomes at 12-month follow-up.
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    Effect of four or more antenatal care visits on facility delivery and early postnatal care services utilization in Uganda: a propensity score matched analysis
    (BMC pregnancy and childbirth, 2022) Mwebesa, Edson; Kagaayi, Joseph; Ssebagereka, Anthony; Nakafeero, Mary; Ssenkusu, John M.; Guwatudde, David; Mbona Tumwesigye, Nazarius
    Maternal mortality remains a global public health issue, more predominantly in developing countries, and is associated with poor maternal health services utilization. Antenatal care (ANC) visits are positively associated with facility delivery and postnatal care (PNC) utilization. However, ANC in itself may not lead to such association but due to differences that exist among users (women). The purpose of this study, therefore, is to examine the effect of four or more ANC visits on facility delivery and early PNC and also the effect of facility-based delivery on early PNC using Propensity Score Matched Analysis (PSMA). Methods: The present study utilized the 2016 Uganda Demographic and Health Survey (UDHS) dataset. Women aged 15 – 49 years who had given birth three years preceding the survey were considered for this study. Propensity score-matched analysis was used to analyze the effect of four or more ANC visits on facility delivery and early PNC and also the effect of facility-based delivery on early PNC. Results: The results revealed a significant and positive effect of four or more ANC visits on facility delivery [ATT (Average Treatment Effect of the Treated)=0.118, 95% CI: 0.063 – 0.173] and early PNC [ATT=0.099, 95% CI: 0.076 – 0.121]. It also found a positive and significant effect of facility-based delivery on early PNC [ATT=0.518, 95% CI: 0.489 – 0.547]. Conclusion: Policies geared towards the provision of four or more ANC visits are an effective intervention towards improved facility-based delivery and early PNC utilisation in Uganda.
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    Endothelial Activation, Acute Kidney Injury, and Cognitive Impairment in Pediatric Severe Malaria
    (Critical care medicine, 2020) Ouma, Benson J.; Ssenkusu, John M.; Shabani, Estela; Datta, Dibyadyuti; Opoka, Robert O.; Idro, Richard; Bangirana, Paul; Park, Gregory; Joloba, Moses L.; Kain, Kevin C.; John, Chandy C.; Conroy, Andrea L.
    Evaluate the relationship between endothelial activation, malaria complications, and long-term cognitive outcomes in severe malaria survivors.Prospectively cohort study of children with cerebral malaria, severe malarial anemia, or community children. Mulago National Referral Hospital in Kampala, Uganda.Children 18 months to 12 years old with severe malaria (cerebral malaria, n = 253 or severe malarial anemia, n = 211) or community children (n = 206) were followed for 24 months.Children underwent neurocognitive evaluation at enrollment (community children) or a week following hospital discharge (severe malaria) and 6, 12, and 24 months follow-up. Endothelial activation was assessed at admission on plasma samples (von Willebrand factor, angiopoietin-1 and angiopoietin-2, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, soluble E-Selectin, and P-Selectin). False discovery rate was used to adjust for multiple comparisons. Severe malaria was associated with widespread endothelial activation compared with community children (p < 0.0001 for all markers). Acute kidney injury was independently associated with changes in von Willebrand factor, soluble intercellular adhesion molecule-1, soluble E-Selectin, P-Selectin, and angiopoietin-2 (p < 0.0001 for all). A log10 increase in angiopoietin-2 was associated with lower cognitive z scores across age groups (children < 5, β −0.42, 95% CI, −0.69 to −0.15, p = 0.002; children ≥ 5, β −0.39, 95% CI, −0.67 to −0.11, p = 0.007) independent of disease severity (coma, number of seizures, acute kidney injury) and sociodemographic factors. Angiopoietin-2 was associated with hemolysis (lactate dehydrogenase, total bilirubin) and inflammation (tumor necrosis factor-α, interleukin-10). In children with cerebral malaria who had a lumbar puncture performed, angiopoietin-2 was associated with blood-brain barrier dysfunction, and markers of neuroinflammation and injury in the cerebrospinal fluid (tumor necrosis factor-α, kynurenic acid, tau).These data support angiopoietin-2 as a measure of disease severity and a risk factor for long-term cognitive injury in children with severe malaria.
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    Estimating the Effect and Cost-Effectiveness of Facemasks in Reducing the Spread of the Severe Acute Respiratory Syndrome- Coronavirus 2 (SARS-CoV-2) in Uganda
    (medRxiv., 2020) Nannyonga, Betty K.; Wanyenze, Rhoda K.; Kaleebu, Pontiano; Ssenkusu, John M.; Lutalo, Tom; Makumbi, Fredrick Edward; Kwizera, Arthur; Byakika, Pauline; Kirungi, Willford; Bosa, Henry Kyobe; Ssembatya, Vincent A.; Mwebesa, Henry; Atwine, Diana; Aceng, Jane Ruth; Woldermariam, Yonas Tegegn
    Evidence that face masks provide effective protection against respiratory infections in the community is scarce. However, face masks are widely used by health workers as part of droplet precautions when caring for patients with respiratory infections. It would therefore be reasonable to suggest that consistent widespread use of face masks in the community could prevent further spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2). In this study we examine public face mask wearing in Uganda where a proportion wears masks to protect against acquiring, and the other to prevent from transmitting SARS-CoV-2. The objective of this study was to determine what percentage of the population would have to wear face masks to reduce susceptibility to and infectivity of SARS-COV-2 in Uganda, keeping the basic reproduction number below unity and/or flattening the curve. We used an SEIAQRD model for the analysis. Results show that implementation of facemasks has a relatively large impact on the size of the coronavirus epidemic in Uganda. We find that the critical mask adherence is 5 per 100 when 80% wear face masks. A cost-effective analysis shows that utilizing funds to provide 1 public mask to the population has a per capita compounded cost of USD 1.34. If provision of face masks is done simultaneously with supportive care, the per capita compounded cost is USD 1.965, while for the case of only treatment and no provision of face masks costs each Ugandan USD 4.0579. We conclude that since it is hard to achieve a 100% adherence to face masks, government might consider provision of face masks in conjunction with provision of care.
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    Estimating the Effect and Cost-Effectiveness of Facemasks in Reducing the Spread of the Severe Acute Respiratory Syndrome- Coronavirus 2 (SARS-CoV-2) in Uganda
    (CC-BY-ND 4.0 International license ., 2020) Nannyonga, Betty K.; Wanyenze, Rhoda K.; Kaleebu, Pontiano; Ssenkusu, John M.; Lutalo, Tom; Makumbi, Fredrick Edward; Kwizera, Arthur; Byakika, Pauline; Kirungi, Willford; Kyobe Bosa, Henry; Ssembatya, Vincent A.; Mwebesa, Henry; Atwine, Diana; Aceng, Jane Ruth; Woldermariamç, Yonas Tegegn
    Evidence that face masks provide effective protection against respiratory infections in the community is scarce. However, face masks are widely used by health workers as part of droplet precautions when caring for patients with respiratory infections. It would therefore be reasonable to suggest that consistent widespread use of face masks in the community could prevent further spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARSCoV- 2). In this study we examine public face mask wearing in Uganda where a proportion wears masks to protect against acquiring, and the other to prevent from transmitting SARSCoV- 2. The objective of this study was to determine what percentage of the population would have to wear face masks to reduce susceptibility to and infectivity of SARS-COV-2 in Uganda, keeping the basic reproduction number below unity and/or flattening the curve. We used an SEIAQRD model for the analysis
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    Infodemic: How an Epidemic of Misinformation Could Lead to a High Number of the Novel Corona Virus Disease Cases in Uganda
    (Preprints, 2020) Nannyonga, Betty K.; Wanyeze, Rhoda K.; Kaleebu, Pontiano; Ssenkusu, John M.; Ssengooba, Freddie; Lutalo, Tom; Kirungi, Willford; Makumbi, Fredrick Edward; Bosa, Henry Kyobe; Ssembatya, Vincent A.; Mwebesa, Henry; Atwine, Diana; Aceng, Jane Ruth; Woldermariam, Yonas Tegegn
    Misinformation during the COVID-19 outbreak has shaped our perception of the disease. Some people thinkthe disease is a bioweapon while others are convinced that it is a hoax. Heightened anxiety often producesfearful rumors, some of which are absurd while others seem plausible and are laced with some truths. But, how does misinformation affect disease spread? In this paper, we construct a mathematical model parameterized by Ugandan data, to study the effect of misinformation on community COVID-19 spread. The analysis shows that misinformation leads to high number of COVID-19 cases in a community, and the effect is highest in the rumour initiators and spreaders. This analysis underscores the importance of addressing misinformation in COVID risk communication.
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    Neurocognitive Function Among Hivinfected Children On Protease Inhibitor -Based Versus Non-Protease Inhibitor Based Antiretroviral Therapy In Uganda: A Pilot Study
    (BMC pediatric, 2021) Nalwanga, Damalie; Musiime, Victor; Bangirana, Paul; Nishiguchi, Erika Phelps; Kiggwe, Andrew; Ssesanga, Titus; Ssenkusu, John M.; Musoke, Philippa; Cusick, Sarah E.
    HIV infection is associated with significant neurocognitive deficits making maximization of cognitive function among children receiving antiretroviral therapy (ART) a public health imperative. Non-protease inhibitors (non-PIs) achieve higher drug levels in the cerebral spinal fluid (CSF) compared to PIs, potentially leading to better neurocognitive function by reducing CSF viral load and inflammation. ART that maximises children’s neurodevelopment and school achievement could result in improved quality of life and productivity as adults, but little research to date has examined whether non-PI ART is associated with better neurocognitive outcomes. We compared the neurocognitive function between children living with HIV receiving PI-based and non PI-based ART.We recruited a consecutive sample of clinically stable Ugandan children living with HIV aged 5–12 years who received PI-based or non PI-based ART for ≥ 1 year (viral load < 1000 copies). Neurocognitive function was assessed using the Kaufman Assessment Battery for Children, the Test of Variables of Attention, and Bruininks-Oseretsky Test of Motor Proficiency. Age-adjusted neurocognitive z-scores for the two groups were compared using linear regression models in STATA version 13. The Hommel’s method was used to adjust for multiple testing.We enrolled 76 children living with HIV; 34 on PI ART and 42 on non-PI ART. Mean (±SD) age was greater in the non-PI vs. PI group (9.5 ± 1.9 vs. 8.5 ± 2.0) years (p = 0.03). Children in the non-PI group had lower socioeconomic scores (5.7 ± 3.3 vs. 7.4 ± 2.8, p = 0.02). There was no difference in neurocognitive function between the groups (adjusted p > 0.05) for KABC and TOVA. Children in the PI group had better total BOT scores than their counterparts (46.07 ± 1.40) vs. 40.51 (1.24), p = 0.03).We detected no difference in neurocognitive function among children on PI and non PI-based ART therapy based on KABC and TOVA tests. Children on PI based ART had better motor function than their counterparts. We recommend a prospective study with a larger sample size.
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    Parenteral Artemisinins Are Associated With Reduced Mortality And Neurologic Deficits And Improved Long-Term Behavioral Outcomes In Children With Severe Malaria
    (BMC medicine, 2021) Conroy, Andrea L.; Opoka, Robert O.; Bangirana, Paul; Namazzi, Ruth; Okullo, Allen E.; Georgieff, Michael K.; Cusick, Sarah; Idro, Richard; Ssenkusu, John M.; John, Chandy C.
    In 2011, the World Health Organization recommended injectable artesunate as the first-line therapy for severe malaria (SM) due to its superiority in reducing mortality compared to quinine. There are limited data on long-term clinical and neurobehavioral outcomes after artemisinin use for treatment of SM.From 2008 to 2013, 502 Ugandan children with two common forms of SM, cerebral malaria and severe malarial anemia, were enrolled in a prospective observational study assessing long-term neurobehavioral and cognitive outcomes following SM. Children were evaluated a week after hospital discharge, and 6, 12, and 24 months of follow-up, and returned to hospital for any illness. In this study, we evaluated the impact of artemisinin derivatives on survival, post-discharge hospital readmission or death, and neurocognitive and behavioral outcomes over 2 years of follow-up.346 children received quinine and 156 received parenteral artemisinin therapy (artemether or artesunate). After adjustment for disease severity, artemisinin derivatives were associated with a 78% reduction in in-hospital mortality (adjusted odds ratio, 0.22; 95% CI, 0.07–0.67). Among cerebral malaria survivors, children treated with artemisinin derivatives also had reduced neurologic deficits at discharge (quinine, 41.7%; artemisinin derivatives, 23.7%, p=0.007). Over a 2-year follow-up, artemisinin derivatives as compared to quinine were associated with better adjusted scores (negative scores better) in internalizing behavior and executive function in children irrespective of the age at severe malaria episode. After adjusting for multiple comparisons, artemisinin derivatives were associated with better adjusted scores in behavior and executive function in children <6 years of age at severe malaria exposure following adjustment for child age, sex, socioeconomic status, enrichment in the home environment, and the incidence of hospitalizations over follow-up. Children receiving artesunate had the greatest reduction in mortality and benefit in behavioral outcomes and had reduced inflammation at 1-month follow-up compared to children treated with quinine.Treatment of severe malaria with artemisinin derivatives, particularly artesunate, results in reduced in-hospital mortality and neurologic deficits in children of all ages, reduced inflammation following recovery, and better long-term behavioral outcomes. These findings suggest artesunate has long-term beneficial effects in children surviving severe malaria.
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    The Ugandan Severe Acute Respiratory Syndrome -Coronavirus 2 (SARS-CoV-2) Model: A Data Driven Approach to Estimate Risk
    (medRxiv, 2020) Nannyonga, Betty; Kyobe Bosa, Henry; Woldermariam, Yonas T.; Kaleebu, Pontiano; Ssenkusu, John M.; Lutalo, Tom; Kirungi, Willford; Makumbi, Fredrick E.; Ssembatya, Vincent A.; Mwebesa, Henry G.; Atwine, Diana; Aceng, Jane R.; Wanyenze, Rhoda K.
    The first case of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) was identified on March 21, 2020, in Uganda. The number of cases increased to 8,287 by September 30, 2020. By May throughout June, most of the cases were predominantly imported cases of truck drivers from neighbouring countries. Uganda responded with various restrictions and interventions including lockdown, physical distancing, hand hygiene, and use of face masks in public, to control the growth rate of the outbreak. By end of September 2020, Uganda had transitioned into community transmissions and most of the reported cases were locals contacts and alerts. This study assessed risks associated with SARS-CoV-2 in Uganda, and presents estimates of the reproduction ratio in real time. An optimal control analysis was performed to determine how long the current mitigation measures such as controlling the exposure in communities, rapid detection, confirmation and contact tracing, partial lockdown of the vulnerable groups and control at the porous boarders, could be implemented and at what cost. Methods: The daily confirmed cases of SARS-CoV-2 in Uganda were extracted from publicly available sources. Using the data, relative risks for age, gender, and geographical location were determined. Four approaches were used to forecast SARS-CoV-2 in Uganda namely linear exponential, nonlinear exponential, logistic and a deterministic model.