Malaria parasites invade red blood cells (RBCs), consume copious amounts of hemoglobin, and severely disrupt iron regulation in humans. Anemia often accompanies malaria disease; however, iron ...supplementation therapy inexplicably exacerbates malarial infections. Here we found that the iron exporter ferroportin (FPN) was highly abundant in RBCs, and iron supplementation suppressed its activity. Conditional deletion of the
gene in erythroid cells resulted in accumulation of excess intracellular iron, cellular damage, hemolysis, and increased fatality in malaria-infected mice. In humans, a prevalent
mutation, Q248H (glutamine to histidine at position 248), prevented hepcidin-induced degradation of FPN and protected against severe malaria disease.
Q248H appears to have been positively selected in African populations in response to the impact of malaria disease. Thus, FPN protects RBCs against oxidative stress and malaria infection.
Serosurveys are a valuable surveillance tool because they provide a more direct measure of population immunity to infectious diseases, such as measles and rubella, than vaccination coverage ...estimates. However, there is concern that serological surveys are costly. We adapted a framework to capture the costs associated with conducting a serosurvey in Zambia.
We costed a nested serosurvey in Southern Province, Zambia that collected dried blood spots from household residents in a post-campaign vaccine coverage survey. The financial costs were estimated using an ingredients-based costing approach. Inputs included personnel, transportation, field consumable items, social mobilization, laboratory supplies, and capital items, and were classified by serosurvey function (survey preparation, data collection, biospecimen collection, laboratory testing, and coordination). Inputs were stratified by whether they were applicable to surveys in general or attributable specifically to serosurveys. Finally, we calculated the average cost per cluster and participant.
We estimated the total nested serosurvey cost was US $68,558 to collect dried blood spots from 658 participants in one province in Zambia. A breakdown of the cost by serosurvey phase showed data collection accounted for almost one third of the total serosurvey cost (32%), followed by survey preparation (25%) and biospecimen collection (20%). Analysis by input categories indicated personnel costs were the largest contributing input to overall serosurvey costs (51%), transportation was second (23%), and field consumables were third (9%). By combining the serosurvey with a vaccination coverage survey, there was a savings of $43,957. We estimated it cost $4,285 per average cluster and $104 per average participant sampled.
Adding serological specimen collection to a planned vaccination coverage survey provided a more direct measurement of population immunity among a wide age group but increased the cost by approximately one-third. Future serosurveys could consider ways to leverage existing surveys conducted for other purposes to minimize costs.
Early infant diagnosis (EID) and treatment can prevent much of the HIV-related morbidity and mortality experienced by children but is challenging to implement in sub-Saharan Africa. Point-of-care ...(PoC) testing would decentralize testing and increase access to rapid diagnosis. The objective of this study was to determine the cost-effectiveness of PoC testing in Southern Province, Zambia.
A decision tree model was developed to compare health outcomes and costs between the standard of care (SoC) and PoC testing using GeneXpert and m-PIMA platforms. The primary health outcome was antiretroviral treatment (ART) initiation within 60 days of sample collection. Additional outcomes included ART initiation by 12 months of age and death prior to ART initiation. Costs included both capital and recurrent costs. Health outcomes and costs were combined to create incremental cost effectiveness ratios (ICERs).
The proportion of children initiating ART within 60 days increased from 27.8% with SoC to 79.8-82.8% with PoC testing depending on the algorithm and platform. The proportion of children initiating ART by 12 months of age increased from 50.9% with SoC to 84.0-86.5% with PoC testing. The proportion of HIV-infected children dying prior to ART initiation decreased from 18.1% with SoC to 3.8-4.6% with PoC testing. Total program costs were similar for the SoC and GeneXpert but higher for m-PIMA. ICERs for PoC testing were favorable, ranging from $23-1,609 for ART initiation within 60 days, $37-2,491 for ART initiation by 12 months of age, and $90-6,188 for deaths prior to ART initiation. Factors impacting the costs of PoC testing, including the lifespan of the testing instruments and integrated utilization of PoC platforms, had the biggest impact on the ICERs. Integrating utilization across programs decreased costs for the EID program, such that PoC testing was cost-saving in some situations.
PoC testing has the potential to improve linkage to care and ART initiation for HIV-infected infants and should be considered for implementation within EID programs to achieve equity in access to HIV services and reduce HIV-related pediatric morbidity and mortality.
Despite significant gains in the past 10 years in the treatment and care of children and adolescents with HIV infection, there is still need for advocacy for this group. The author discusses how far ...we have come and the need for on‐going efforts, not only for appropriate child‐friendly drug formulations, but also for cooperation between quantitative and qualitative scientists to further the existing knowledge base of how best to help these children with a chronic disease.
Delay in receiving treatment for uncomplicated malaria (UM) is often reported to increase the risk of developing severe malaria (SM), but access to treatment remains low in most high-burden areas. ...Understanding the contribution of treatment delay on progression to severe disease is critical to determine how quickly patients need to receive treatment and to quantify the impact of widely implemented treatment interventions, such as 'test-and-treat' policies administered by community health workers (CHWs). We conducted a pooled individual-participant meta-analysis to estimate the association between treatment delay and presenting with SM.
A search using Ovid MEDLINE and Embase was initially conducted to identify studies on severe Plasmodium falciparum malaria that included information on treatment delay, such as fever duration (inception to 22nd September 2017). Studies identified included 5 case-control and 8 other observational clinical studies of SM and UM cases. Risk of bias was assessed using the Newcastle-Ottawa scale, and all studies were ranked as 'Good', scoring ≥7/10. Individual-patient data (IPD) were pooled from 13 studies of 3,989 (94.1% aged <15 years) SM patients and 5,780 (79.6% aged <15 years) UM cases in Benin, Malaysia, Mozambique, Tanzania, The Gambia, Uganda, Yemen, and Zambia. Definitions of SM were standardised across studies to compare treatment delay in patients with UM and different SM phenotypes using age-adjusted mixed-effects regression. The odds of any SM phenotype were significantly higher in children with longer delays between initial symptoms and arrival at the health facility (odds ratio OR = 1.33, 95% CI: 1.07-1.64 for a delay of >24 hours versus ≤24 hours; p = 0.009). Reported illness duration was a strong predictor of presenting with severe malarial anaemia (SMA) in children, with an OR of 2.79 (95% CI:1.92-4.06; p < 0.001) for a delay of 2-3 days and 5.46 (95% CI: 3.49-8.53; p < 0.001) for a delay of >7 days, compared with receiving treatment within 24 hours from symptom onset. We estimate that 42.8% of childhood SMA cases and 48.5% of adult SMA cases in the study areas would have been averted if all individuals were able to access treatment within the first day of symptom onset, if the association is fully causal. In studies specifically recording onset of nonsevere symptoms, long treatment delay was moderately associated with other SM phenotypes (OR 95% CI >3 to ≤4 days versus ≤24 hours: cerebral malaria CM = 2.42 1.24-4.72, p = 0.01; respiratory distress syndrome RDS = 4.09 1.70-9.82, p = 0.002). In addition to unmeasured confounding, which is commonly present in observational studies, a key limitation is that many severe cases and deaths occur outside healthcare facilities in endemic countries, where the effect of delayed or no treatment is difficult to quantify.
Our results quantify the relationship between rapid access to treatment and reduced risk of severe disease, which was particularly strong for SMA. There was some evidence to suggest that progression to other severe phenotypes may also be prevented by prompt treatment, though the association was not as strong, which may be explained by potential selection bias, sample size issues, or a difference in underlying pathology. These findings may help assess the impact of interventions that improve access to treatment.
Insecticide-treated nets (ITNs) reduce malaria morbidity and mortality in endemic areas. Despite increasing availability, the use of ITNs remains limited in some settings. Poor malaria knowledge is a ...barrier to the widespread use of ITNs. The goal of this study was to assess the levels of malaria knowledge and evaluate factors associated with bed net use among individuals residing in three regions of southern Africa with different levels of malaria transmission and control.
A cross-sectional study was conducted on a sample of 7535 residents recruited from 2066 households in Mutasa District, Zimbabwe (seasonal malaria transmission), Choma District, Zambia (low transmission) and Nchelenge District, Zambia (high transmission), between March 2012 and March 2017. A standardized questionnaire was used to collect data on demographics, malaria-related knowledge and use of preventive measures. Multivariate logistic regression analyses were used to assess determinants of bed net use.
Most of the 3836 adult participants correctly linked mosquito bites to malaria (85.0%), mentioned at least one malaria symptom (95.5%) and knew of the benefit of sleeping under an ITN. Bed net ownership and use were highest in Choma and Nchelenge Districts and lowest in Mutasa District. In multivariate analyses, knowledge of ITNs was associated with a 30-40% increased likelihood of bed net use after adjusting for potential confounders across all sites. Other factors significantly associated with bed net use were age, household size and socioeconomic status, although the direction, strength and size of association varied by study site. Importantly, participants aged 5-14 years had reduced odds of sleeping under a bed net compared to children younger than 5 years.
Relevant knowledge of ITNs translated into the expected preventive behaviour of sleeping under a bed net, underscoring the need for continued health messaging on malaria prevention. The implementation and delivery of malaria control and elimination interventions needs to consider socioeconomic equity gaps, and target school-age children to ensure access to and improve utilization of ITNs.
Pediatric Symptom Checklist-17 Li, Nan; Tan, Mei; Thuma, Philip E. ...
European journal of psychological assessment : official organ of the European Association of Psychological Assessment,
05/2023, Letnik:
39, Številka:
3
Journal Article
Recenzirano
This study aimed to investigate the psychometric
properties of the Pediatric Symptom Checklist-17 (PSC-17) in a sample of
children orphaned or made vulnerable (OVC) by HIV in Zambia. Caregivers of ...1,076
OVC (55.1% boys; Mage = 12.91 years) completed the
PSC-17. Competing models, including confirmatory factor analysis (CFA),
hierarchical CFA, bifactor CFA, exploratory structural equation modeling (ESEM),
and bifactor ESEM, were tested to evaluate the optimal factor structure of the
PSC-17. Results showed that the bifactor ESEM provided the best approximation of
the PSC-17 data with a well-defined general psychosocial problems factor
explaining 72% of the reliable variance in the total score and an internalizing
factor containing 63% of the reliable variance unique from the general factor.
The observed overall psychosocial problems score was associated with lower
academic achievement and working memory (with small effect sizes), supporting
the discriminant validity of score interpretation. Results of multiple
indicators multiple causes (MIMIC) analyses revealed that all items functioned
equivalently across child gender and age.
Studies focusing on children affected by HIV have shown that they have generally lower academic performance, however, few studies separate children who are HIV exposed and infected (CHEI) and those ...who are HIV exposed but uninfected (CHEU). Importantly, in rural sub-Saharan Africa, the majority of studies on CHEI and CHEU examine academic performance indirectly based on cognitive test scores. Therefore, studies assessing the effects of HIV on academic achievement directly for CHEI and CHEU are needed. This article evaluates the effects of HIV-infection on cognitive and academic performance by comparing CHEI (n = 82) and CHEU (n = 1045) aged 7-17 years old using cross-sectional data from an ongoing longitudinal study in a rural area of Zambia. Youth completed cognitive and academic assessments; their height and weight were assessed to generate Body Mass Index (BMI). Caregiver questionnaires provided information on youths' years in school and household socio-economic status (SES). Results indicated that while HIV infection status did explain some of the variance in performance between CHEI and CHEU, age, BMI, years of schooling and SES accounted for additional variance. The effect of years of schooling on both cognitive and academic performance demonstrated that CHEI's performance may be greatly improved by consistent school enrollment.
Obtaining accurate malaria surveillance data is challenging in low-transmission settings because large sample sizes are required to estimate incidence and prevalence precisely. Serology is an ...additional tool to document progress toward malaria elimination. An enzyme immunoassay to Plasmodium falciparum lysate was used to estimate age-specific seroprevalence among residents of southern Zambia, where malaria transmission has declined to pre-elimination levels during the past two decades. Plasma was eluted from 3,362 dried blood spots collected during five cross-sectional surveys conducted between 2009 and 2012, and again in 2018. Annual seroconversion rates (SCRs), an estimate of the force of infection, were calculated using a reversible catalytic model. The SCR decreased by two thirds from a level of approximately 0.15/year in 2009 and 2010 to approximately 0.05/year in 2011 and 2012, and then decreased 5-fold to 0.01/year by 2018, demonstrating the utility of serology in documenting progress toward elimination.
In 2017, 64% of children living with HIV in Zambia accessed Antiretroviral Therapy (ART). Despite expanded ART coverage, there is paucity of information on effectiveness of pediatric ART in reducing ...mortality. The aim of this research is to describe treatment outcomes, measure mortality rates and assess predictors of mortality among children receiving ART.
Using a retrospective cohort study design, we abstracted routinely collected clinical data from medical records of children from birth to 15 years old, who had received ART for at least 6 months at Livingstone Central Hospital in Southern Province Zambia, between January 2003 and June 2015. The primary outcome was death. Cause of death was ascertained from medical records and death certificates. Distribution of survival times according to baseline covariates were estimated using Kaplan Meier and Cox Proportional Hazards methods.
Overall, 1039 children were commenced on ART during the study period. The median age at treatment initiation was 3.6 years (IQR: 1.3-8.6) and 520 (50%) children were female. Of these, 71 (7%) died, 164 (16%) were lost to follow-up, 210 (20%) transferred and 594 (56%) were actively on treatment. After 4450 person years, mortality rate was 1.6/100 (95% CI: 1.4-1.8). Mortality was highest during the first 3 months of treatment (11.7/100 (95% CI: 7.6-16.3). In multivariable proportional hazards regression, the adjusted hazards of death were highest among children aged < 1 year (aHR = 3.1 (95% CI: 1.3-6.4), compared to those aged 6-15 years, WHO stage 4 (aHR =4.8 (95% CI: 2.3-10), compared to WHO stage 1 and 2. In the sensitivity analysis to address bias due to loss to follow-up, mortality increased 5 times when we assumed that all the children who were lost to follow up died within 90 days of their last visit.
We observed low attrition due to mortality among children on ART. Loss to follow-up was high (16%). Mortality was highest during the first 3 months of treatment. Children aged less than one year and those with advanced WHO disease stage had higher mortality. We recommend effective interventions to improve retention in care and early diagnosis of HIV in children.
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