Expanding Praziquantel (PZQ) Access beyond Mass Drug Administration Programs: Paving a Way Forward for a Pediatric PZQ Formulation for Schistosomiasis.

Treating preschool age children (PSAC) with schistosomiasis remains a challenge. Without a pediatric praziquantel (PZQ) formulation, the inclusion of this age group in control programs is limited, and general access to treatment in routine care settings is severely bottlenecked. There are, however, current platforms that target PSAC in primary health care such as the integrated management of childhood illnesses (IMCI), which could integrate PZQ in their portfolio and deliver a pediatric PZQ formulation when available. In addition, other age groups such as school-aged children (SAC) could also benefit from the IMCI’s successful strategy and be treated in health centers using a similar approach. This Viewpoint article reports a summary of a symposium held at the American Society of Tropical Medicine and Hygiene national meeting in 2014 that brought together six experts in different areas in the field of pediatric schistosomiasis to form a working group that could provide recommendations for the inclusion of PSAC in the IMCI and other existing preschool outreach programs. This was to develop and adapt methodologies to fill existing gaps left by current mass drug administration (MDA) programs and synergize efforts for schistosomiasis control more broadly. Foremost, this includes a better definition of subclinical disease in young children to integrate into ICMI guidelines and further demonstration of the benefit of expanded access of treatment to children of all ages by encouraging universal access

Toxic Stress and Quality of Life in Early School‐Aged Ugandan Children With and Without Perinatal Human Immunodeficiency Virus Infection

Caregiver’s and child’s self‐reported quality of life (QOL) was defined using standardized questionnaires in a sample (N = 277) of 6–10 years old HIV‐infected, HIV‐exposed uninfected, and HIV‐unexposed uninfected children from Uganda. Psychosocial stress (acute stress and cumulative lifetime adversity) and physiologic stress (dysregulations across 13 biomarkers), perinatal HIV status, and their interaction were related to child QOL via general linear models. Lower child‐ and caregiver‐reported psychosocial stress were dose‐dependently associated with higher QOL (acute stress: mean difference coefficient b = 8.1–14.8, effect size [ES] = 0.46–0.83). Lower allostasis was dose‐dependently associated with higher QOL (b = 6.1–9.7, ES = 0.34–0.54). Given low caregiver acute stress, QOL for HIV‐infected was similar to HIV‐uninfected children; however, given high caregiver acute stress, a QOL disadvantage (b = −7.8, 95% CI: −12.8, −2.8; ES = −0.73) was evident for HIV‐infected versus uninfected children. Testing of caregiver stress reduction interventions is warranted to increase wellbeing in dependent children.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156459/2/cad20355.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156459/1/cad20355_am.pd

Multivitamin supplementation in HIV infected adults initiating antiretroviral therapy in Uganda: the protocol for a randomized double blinded placebo controlled efficacy trial.

BACKGROUND: Use of multivitamin supplements during the pre-HAART era has been found to reduce viral load, enhance immune response, and generally improve clinical outcomes among HIV-infected adults. However, immune reconstitution is incomplete and significant mortality and opportunistic infections occur in spite of HAART. There is insufficient research information on whether multivitamin supplementation may be beneficial as adjunct therapy for HIV-infected individuals taking HAART. We propose to evaluate the efficacy of a single recommended daily allowance (RDA) of micronutrients (including vitamins B-complex, C, and E) in slowing disease progression among HIV-infected adults receiving HAART in Uganda. METHODS/DESIGN: We are using a randomized, double-blind, placebo-controlled trial study design. Eligible patients are HIV-positive adults aged at least 18 years, and are randomized to receive either a placebo; or multivitamins that include a single RDA of the following vitamins: 1.4 mg B1, 1.4 mg B2, 1.9 mg B6, 2.6 mcg B12, 18 mg niacin, 70 mg C, 10 mg E, and 0.4 mg folic acid. Participants are followed for up to 18 months with evaluations at baseline, 6, 12 and 18 months. The study is primarily powered to examine the effects on immune reconstitution, weight gain, and quality of life. In addition, we will examine the effects on other secondary outcomes including the risks of development of new or recurrent disease progression event, including all-cause mortality; ARV regimen change from first- to second-line therapy; and other adverse events as indicated by incident peripheral neuropathy, severe anemia, or diarrhea. DISCUSSIONS: The conduct of this trial provides an opportunity to evaluate the potential benefits of this affordable adjunct therapy (multivitamin supplementation) among HIV-infected adults receiving HAART in a developing country setting. TRIAL REGISTRATION: Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01228578

Caregiver socioemotional health as a determinant of child wellâ being in schoolâ aged and adolescent Ugandan children with and without perinatal HIV exposure

ObjectiveCaregiver socioâ emotional attributes are major determinants of child wellâ being. This investigation in vulnerable schoolâ aged Ugandan children estimates relationships between children’s wellâ being and their caregiver’s anxiety, depression and social support.MethodsPerinatally HIVâ infected, HIVâ exposed uninfected and HIVâ unexposed Ugandan children and their caregivers were enrolled. Perinatal HIV status was determined by 18 months of age using DNAâ polymerase chainâ reaction test; status was confirmed via HIV rapid diagnostic test when children were 6â 18 years old. Five indicators of child wellâ being (distress, hopelessness, positive future orientation, esteem and quality of life (QOL)) and caregiversâ socioemotional status (depressive symptoms, anxiety and social support) were measured using validated, culturally adapted and translated instruments. Categories based on tertiles of each caregiver psychosocial indicator were defined. Linear regression analyses estimated percent differences (β) and corresponding 95% confidence intervals (CI) for child wellâ being in relation to caregiver’s psychosocial status.ResultsAs per tertile increment, caregiver anxiety was associated with 2.7% higher distress (95%CI:0.2%, 5.3%) and lower selfâ esteem/QOL (β = â 1.3%/â 2.6%; 95%CI: â 5.0%,â 0.2%) in their children. Child distress/hopelessness increased (β = 3.3%/7.6%; 95%CI:0.4%, 14.7%) and selfâ esteem/QOL decreased 2.3% (β = â 2.3%/â 4.4%; 95%CI: â 7.2%, â 1.3%) as per tertile increment in caregiver depression. Higher caregiver social support was associated with lower distress and higher positive outlook (β = 3%; 95%CI:1.4%, 4.5%) in their children. HIVâ infected/exposed children had most caregiver depressionâ related QOL deficit (β = â 5.2%/â 6.8%; 95%CI: â 12.4%, â 0.2%) and HIVâ unexposed children had most caregiver social supportâ related enhancements in positive outlook (β=4.5%; 95%CI:1.9%, 7.1%).ConclusionsCaregiver anxiety, depressive symptoms and low social support were associated with worse wellâ being in schoolâ aged and adolescent children. Improvement of caregiver mental health and strengthening caregiver social support systems may be a viable strategy for improving wellâ being of vulnerable children and adolescents in this setting.ObjectifLes attributs socioâ affectifs des responsables d’enfants sont des déterminants majeurs du bienâ être des enfants. Cette investigation menée auprès d’enfants ougandais vulnérables dâ âge scolaire a estimé les relations entre le bienâ être des enfants et l’anxiété, la dépression et le soutien social de leur responsable.MéthodesDes enfants ougandais infectés par le VIH de manière périnatale, exposés au VIH mais non infectés, et non exposés au VIH ainsi que leurs responsables ont été inscrits. Le statut VIH périnatal a été déterminé à lâ âge de 18 mois à l’aide du test de PCR de lâ ADN; le statut a été confirmé par un test de diagnostic rapide du VIH chez les enfants âgés de 6 à 18 ans. Cinq indicateurs du bienâ être de l’enfant (détresse, désespoir, orientation future positive, estime et qualité de vie (QV)), et le statut psychosocial des responsables (symptômes dépressifs, anxiété et soutien social) ont été mesurés à l’aide de méthodes validées, adaptées à la culture et respectées et d’outils traduits. Des catégories basées sur les tertiles de chaque indicateur psychosocial du responsable ont été définies. Des analyses de régression linéaire ont estimé les différences en pourcentage (β) et les intervalles de confiance (IC) à 95% correspondants pour le bienâ être de l’enfant par rapport au statut psychosocial de leurs responsables.RésultatsPar incrément de tertile, l’anxiété des responsables était associé à 2,7% de détresse plus élevé (IC95%: 0,2%, 5,3%) et de faible estime de soi/QV (β = â 1,3%/â 2,6%; IC95%: â 5,0%, â 0,2%) chez leurs enfants. La détresse et le désespoir des enfants augmentaient (β = 3,3%/7,6%; IC95%: 0,4%, 14,7%) et l’estime de soi/QV diminuait de 2,3% (β = â 2,3%/â 4,4%; IC95%: â 7,2%, â 1,3%) par incrément de tertile de la dépression chez le responsable. Un soutien social plus élevé des responsables était associé à une détresse moindre et à une perspective positive plus élevée (β = 3%; IC95%: 1,4%, 4,5%) chez leurs enfants. Les enfants infectés/exposés au VIH présentaient pour la plupart un déficit de QV lié à la dépression de leurs responsables (β = â 5,2%/â 6,8%; IC95%: â 12,4%, â 0,2%), et ceux non exposés au VIH présentaient pour la plupart des améliorations en perspective positive liées au soutien social de leurs responsables (β = 4,5%; IC95%: 1,9%, 7,1%).ConclusionsL’anxiété, les symptômes dépressifs et un faible soutien social du responsable étaient associés à un bienâ être précaire chez les enfants dâ âge scolaire et les adolescents. L’amélioration de la santé mentale des responsables et le renforcement des systèmes de soutien social pour les responsables peuvent constituer une stratégie viable pour améliorer le bienâ être des enfants et des adolescents vulnérables dans cette région.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149358/1/tmi13221.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149358/2/tmi13221_am.pd

Cognitive deficits and educational loss in children with schistosome infection-A systematic review and meta-analysis.

BACKGROUND: By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits. METHODOLOGY/PRINCIPAL FINDINGS: This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains-learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5-19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28, 95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The significance of infection-associated deficits in scholastic achievement was sensitive to ROB. Schistosoma infection-related deficits in learning and memory tests were invariant by ROB and study design. CONCLUSION/SIGNIFICANCE: Schistosoma infection/non-treatment was significantly associated with educational, learning, and memory deficits in SAC. Early treatment of children in Schistosoma-endemic regions could potentially mitigate these deficits. TRIAL REGISTRATION: ClinicalTrials.gov CRD42016040052

Depressive and Anxiety Symptoms Predict Sustained Quality of Life Deficits in HIV-Positive Ugandan Adults Despite Antiretroviral Therapy: A Prospective Cohort Study

Abstract The impact of psychosocial status at onset of antiretroviral therapy on changes in quality of life (QOL) and subjectively rated health (SRH) among adults on highly active antiretroviral therapy (HAART) in resource-limited settings is poorly understood. Therefore, we evaluate the association between stigma, anxiety, depression, and social support and change in QOL and SRH in HIV-infected Ugandan adults during an 18-month period. Psychosocial indicators were assessed at enrollment using structured questionnaires. QOL and SRH measures were assessed at months 0, 6, 12, and 18 using the Medical Outcomes Survey-HIV. Linear mixed models determined risk estimated differences in QOL and SRH in relation to quartiles of each psychosocial status indicator. Repeated measures generalized estimating equations modeling was implemented to assess differences in likelihood of improved versus nonimproved SRH during follow-up. QOL scores and SRH improved significantly for all participants over 18 months (P < 0.0001). The gain in QOL increased dose-dependently as baseline depressive symptoms (time∗depression P < 0.001) and anxiety levels (time∗anxiety P < 0.001) declined. Lower social support was associated with worse QOL at baseline (P = 0.0005) but QOL improvement during follow-up was not dependent on baseline level of social support (time∗social support P = 0.8943) or number of stigmatizing experiences (time∗stigma P = 0.8662). Psychosocial determinants did not predict changes in SRH in this study. High levels of depression and anxiety symptoms at HAART initiation predicts lower gains in QOL for HIV-positive patients for as long as 18 months. Long-term QOL improvements in HIV-infected adults may be enhanced by implementation of psychosocial interventions to reduce depression and anxiety in HIV-infected adults

SCORE studies on the impact of drug treatment on morbidity due to <i>Schistosoma mansoni</i> and <i>Schistosoma haematobium</i> infection

The Schistosomiasis Consortium for Operational Research (SCORE) was funded in 2008 to improve the evidence base for control and elimination of schistosomiasis-better understanding of the systemic morbidities experienced by children in schistosomiasis-endemic areas and the response of these morbidities to treatment, being essential for updating WHO guidelines for mass drug administration (MDA) in endemic areas. This article summarizes the SCORE studies that aimed to gauge the impact of MDA-based treatment on schistosomiasis-related morbidities. Morbidity cohort studies were embedded in the SCORE's larger field studies of gaining control of schistosomiasis in Kenya and Tanzania. Following MDA, cohort children had less undernutrition, less portal vein dilation, and increased quality of life in Year 5 compared with baseline. We also conducted a pilot study of the Behavioral Assessment System for Children (BASC-2) in conjunction with the Kenya gaining control study, which demonstrated beneficial effects of treatment on classroom behavior. In addition, the SCORE's Rapid Answers Project performed systematic reviews of previously available data, providing two meta-analyses related to morbidity. The first documented children's infection-related deficits in school attendance and achievement and in formal tests of learning and memory. The second showed that greater reductions in egg output following drug treatment correlates significantly with reduced odds of most morbidities. Overall, these SCORE morbidity studies provided convincing evidence to support the use of MDA to improve the health of school-aged children in endemic areas. However, study findings also support the need to use enhanced metrics to fully assess and better control schistosomiasis-associated morbidity

Treatment for Schistosoma japonicum, Reduction of Intestinal Parasite Load, and Cognitive Test Score Improvements in School-Aged Children

Parasitic worm infections are associated with cognitive impairment and lower academic achievement for infected relative to uninfected children. However, it is unclear whether curing or reducing worm infection intensity improves child cognitive function. We examined the independent associations between: (i) Schistosoma japonicum infection-free duration, (ii) declines in single helminth species, and (iii) joint declines of ≥2 soil-transmitted helminth (STH) infections and improvements in four cognitive tests during18 months of follow-up. Enrolled were schistosome-infected school-aged children among whom coinfection with STH was common. All children were treated for schistosome infection only at enrolment with praziquantel. Children cured or schistosome-free for >12 months scored higher in memory and verbal fluency tests compared to persistently infected children. Likewise, declines of single and polyparasitic STH infections predicted higher scores in three of four tests. We conclude that reducing the intensity of certain helminth species and the frequency of multi-species STH infections may have long-term benefits for affected children's cognitive performance. The rapidity of schistosome re-infection and the ubiquity of concurrent multi-species infection highlight the importance of sustained deworming for both schistosome and STH infections to enhance the learning and educational attainment of children in helminth-endemic settings

The Synergistic Effect of Concomitant Schistosomiasis, Hookworm, and Trichuris Infections on Children's Anemia Burden

Polyparasitic infections have been recognized as the norm in many tropical developing countries, but the significance of this phenomenon for helminth-associated morbidities is largely unexplored. Earlier studies have suggested that multi-species, low-intensity parasitic infections were associated with higher odds of anemia among school-age children relative to their uninfected counterparts or those with one low-intensity infection. However, specific studies of the nature of interactions between helminth species in the mediation of helminth-associated morbidities are lacking. This study quantifies the extent to which polyparasitic infections have more than the sum of adverse effects associated with individual infections in the context of childhood anemia. This study found that the risk of anemia is amplified beyond the sum of risks for individual infections in children simultaneously exposed to 1) hookworm and schistosomiasis, and 2) hookworm and trichuris, and suggests that combined treatment for some geohelminth species and schistosomiasis could yield greater than additive benefits for the reduction of childhood anemia in helminth-endemic areas. However, more studies to understand the full range of interactions between parasitic species in their joint effects on helminth-associated morbidities will be necessary to better predict the impact of any future public health intervention