Asymptomatic Plasmodium infection and cognition among primary schoolchildren in a high malaria transmission setting in Uganda

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Study Justification:
This study aimed to investigate the impact of asymptomatic Plasmodium infection on cognitive function among primary schoolchildren in a high malaria transmission setting in Uganda. Asymptomatic parasitemia is common in these areas, but its effect on cognition is not well understood. Understanding this relationship is important for developing interventions to improve cognitive function in schoolchildren.
Highlights:
– The study included 740 primary schoolchildren in Tororo, Uganda.
– 30% of the children had asymptomatic Plasmodium infection.
– Infected children had lower test scores for abstract reasoning and sustained attention compared to uninfected children.
– There was a dose-response relationship between parasite density and scores for sustained attention.
– No associations were found between anemia and cognition.
– Interventions aimed at reducing the prevalence of asymptomatic parasitemia may have cognitive benefits for schoolchildren in high transmission settings.
Recommendations:
Based on the findings of this study, the following recommendations can be made:
1. Implement interventions to reduce the prevalence of asymptomatic Plasmodium infection among schoolchildren in high transmission settings.
2. Conduct further research to explore the long-term effects of asymptomatic parasitemia on cognitive function.
3. Include cognitive assessments as part of routine health screenings for schoolchildren in malaria-endemic areas.
4. Provide education and awareness programs for parents, teachers, and policymakers about the potential impact of asymptomatic parasitemia on cognitive development.
Key Role Players:
1. Ministry of Health: Responsible for implementing interventions and policies related to malaria control and education.
2. Department of Education: Involved in incorporating cognitive assessments into routine health screenings for schoolchildren.
3. Local Health Centers: Provide healthcare services and support for implementing interventions.
4. Schools and Teachers: Play a role in educating parents and students about the impact of asymptomatic parasitemia on cognitive function.
Cost Items for Planning Recommendations:
1. Training and Capacity Building: Budget for training healthcare workers, teachers, and community health workers on malaria control and cognitive assessments.
2. Interventions: Budget for implementing interventions to reduce the prevalence of asymptomatic parasitemia, such as mass distribution of insecticide-treated nets and targeted treatment programs.
3. Awareness Programs: Allocate funds for developing and implementing education and awareness programs for parents, teachers, and policymakers.
4. Monitoring and Evaluation: Set aside resources for monitoring and evaluating the impact of interventions on cognitive function and malaria prevalence among schoolchildren.

The strength of evidence for this abstract is 8 out of 10.
The evidence in the abstract is strong because it is based on a clinical trial with a large sample size (740 children) and includes adjusted mean differences with 95% confidence intervals. The study also provides evidence for a dose-response relationship between parasite density and cognitive scores. To improve the evidence, the abstract could include more information on the methodology, such as the randomization process and blinding procedures.

Asymptomatic parasitemia is common among schoolchildren living in areas of high malaria transmission, yet little is known about its effect on cognitive function in these settings. To investigate associations between asymptomatic parasitemia, anemia, and cognition among primary schoolchildren living in a high malaria transmission setting, we studied 740 children enrolled in a clinical trial in Tororo, Uganda. Parasitemia, measured by thick blood smears, was present in 30% of the children. Infected children had lower test scores for abstract reasoning (adjusted mean difference [AMD] -0.6, 95% confidence interval [CI] -1.01 to -0.21) and sustained attention (AMD -1.6 95% CI -2.40 to -0.81) compared with uninfected children. There was also evidence for a dose-response relationship between parasite density and scores for sustained attention. No associations were observed between anemia and either test of cognition. Schoolchildren in high transmission settings may experience cognitive benefits, from interventions aimed at reducing the prevalence of asymptomatic parasitemia. Copyright © 2013 by The American Society of Tropical Medicine and Hygiene.

The study was conducted in February 2011 in Mulanda primary school located in Mulanda sub-county, Tororo District, eastern Uganda. This area is mainly dry savannah grassland interrupted by bare rocky outcrops and lower lying swamps, although natural vegetation has mostly been replaced by cultivated crops. Tororo District is characterized by a high intensity of malaria transmission,14 with an estimated entomological inoculation rate of 562 infective bites per person per year.15 Transmission is bimodal, with peaks associated with the two rainy seasons. Malaria in the area is predominantly caused by Plasmodium falciparum3 and Anopheles gambiae s.s., and to a lesser extent, Anopheles funestus are the main vectors.15 In the 5 years before this study, malaria control in Tororo District was typically limited to the promotion of IPT during pregnancy, distribution of insecticide-treated nets (ITNs) through antenatal care services and malaria case management with artemisinin-based combined therapy. In January 2011, however, a mass community-based free ITN distribution campaign was conducted throughout the sub-county. Mulanda sub-county has eight primary schools, all of which are under the government supported universal primary education scheme. Mulanda primary school was purposively selected for the study because of its large student population (1,320 students) and close proximity (approximately 500 meters) to the main public health facility in the area (Mulanda Health Center IV). This study reports baseline data collected as part of a randomized placebo-controlled trial investigating the impact of IPT on malaria morbidity and cognitive function in Ugandan schoolchildren (Clinicaltrials.gov identifier {“type”:”clinical-trial”,”attrs”:{“text”:”NCT01231880″,”term_id”:”NCT01231880″}}NCT01231880). All children with parental consent were screened for eligibility to join the study. Children were excluded if they had any of the following: 1) known allergy or prior adverse reaction to artemisinin-based regimens; 2) history of menarche; 3) fever (axillary temperature ≥ 37.5°C) or history of fever in previous 24 hours; 4) evidence of severe malaria or danger signs; or 5) ongoing antimalarial treatment. At enrollment, a standardized questionnaire was administered by study personnel to children fulfilling the selection criteria to record data on socio- demographics, bed-net ownership, and bed-net use. A focused physical examination was conducted that included a general and abdominal examination as well as measurement of temperature and weight. A finger-prick blood sample was obtained for thick and thin blood smears to assess for Plasmodium infection, hemoglobin estimation, and for filter paper storage. Stool samples were also collected. All blood smears were labeled and air dried at the school and subsequently stained with 2% Giemsa for 30 minutes at the health facility at the end of each day. Parasite densities were determined from thick blood smears by counting the number of asexual parasites per 200 white blood cells (or per 500 if the count was < 10 parasites/200 white cells), assuming a white blood cell count of 8,000/mL. A smear was considered negative after reviewing 100 high-powered fields. Asymptomatic malaria was defined as a positive blood smear for Plasmodium parasites with no associated clinical symptoms. All positive thick blood smears had corresponding thin smears viewed for species identification. Gametocytaemia was also determined from thick blood smears. Two independent microscopists read the slides, with a third microscopist resolving discrepant results. Hemoglobin concentration was assessed using a portable hemoglobinometer (HemoCue Ltd., Angelholm, Sweden) and estimated to an accuracy of 1 g/dL. Stool samples were examined microscopically for the eggs of intestinal nematodes and Schistosoma mansoni (the sole cause of schistosomiasis in the study area), using the Kato-Katz technique. Two aspects of cognition were assessed, including sustained attention assessed by a code transmission test and abstract reasoning tested using Ravens matrices. These two tests have been adapted for an African setting and used in a number of previous studies.7,16 The test for sustained attention was adapted from the Tests of Everyday Attention for Children (TEA-Ch)17 and was administered in groups of 15 or less in the local language, Japhadhola, which is also the language of school instruction for children in classes 1–3 in Mulanda sub-county. The test involved listening to a tape and identifying different numbers (code transmission). During the code transmission task, a list of digits was read out aloud at the speed of one per second. Children were required to listen out for a code—“the number 5 repeated twice consecutively”—and then record the two numbers that preceded the code. The test was administered at school over the weekend when there were no active classes at the school to reduce on external interference. Only children invited for the test were present at school on the testing days. Before the test, children were given three warm-up activities to familiarize them with the tape recorder, as well as assess their ability to count and write numbers. During the test of abstract reasoning, a set of geometric figures with a missing pattern was presented to the children and they were asked to identify the missing item that completes a pattern from a group of almost identical alternatives.18 All data were double-entered and cross-checked in a bespoke Microsoft access database (Microsoft Corp., Seattle, WA). Consistency checks were performed and all discrepancies and queries verified against original paper forms. Plasmodium infection was defined on the basis of expert microscopy results and the proportion of children with asymptomatic Plasmodium parasitemia was calculated as the number of children with any parasites (irrespective of species) on thick smear divided by the total number of children enrolled. Parasite density was categorized as above and below 1,000 parasites/μL. Anemia was defined using the World Health Organization (WHO) age-specific thresholds for hemoglobin (< 11.5 g/dL for children 6 to < 12 years of age and < 12.0 g/dL for those 12–14 years of age).19,20 The anthropometric index z-score weight-for-age was calculated using the egen Stata function for standardizing anthropometric measures in children and adolescents.21 Children were classified as underweight if they were less than two standard deviations below the reference mean. A household wealth index was created using principal component analysis of data on household possessions, utilities, and housing construction for each student.22 Households were ranked according to their distribution along the index, which was then divided into quartiles and classified as an ordinal variable for use in multivariate analysis models. Information on maternal education was also included in the analysis, because of its key influence on children's cognition. All statistical analyses were carried out using Stata version 12.0 software (STATA Corporation, College Station, TX). The outcomes of interest were Plasmodium infection and scores in the code transmission and Raven's matrices tests. Ninety-five percent binomial confidence intervals (CI) were estimated for proportions and standard deviations presented for means. Univariable associations between Plasmodium infection and potential risk factors were assessed using logistic regression and all variables showing an association at a 20% significance level were included into a multivariable logistic regression model. Logical model building using both forward and backward elimination was used to generate minimum adequate model using a 5% significance level; however, bed-net use, socioeconomic group, and anemia were retained as fixed terms in the model regardless of statistical significance because of their known association to Plasmodium infection among school-aged children.3,23 To investigate the association between asymptomatic Plasmodium infection and cognitive function, two sets of analyses, one for abstract reasoning (score 0–20) and the second for sustained attention (score 0–20) were undertaken. The effect of explanatory variables was quantified by mean differences in test performance scores using univariable and multivariable linear regression. Case re-sampling bootstrapping was used to account for non-normality of the scores. Variables identified as significant (P < 0.2) in univariate analysis were considered for multivariable analysis. Logical model building using both forward and backward elimination was used to generate minimum adequate models; however, helminth infection, maternal education, and anemia were retained as fixed terms in all models regardless of statistical significance because of their known effect on cognition.24,25 Interaction was assessed on the basis of likelihood ratio test and included in the final model if P ≤ 0.05. Sensitivity analysis explored the influence of parasite density on cognition, with densities categorized as uninfected, infected with 1–999 parasites/μL, and infected with ≥ 1000 parasites/μL. The study protocol was approved by the Makerere University School of Medicine Research and Ethics Committee (#2010-016) and the Uganda National Council of Science and Technology (#HS 865). Before the start of the study, investigators met with elected government representatives and community leaders to inform them of the study and explain the methodology. Written informed consent was obtained from the parents/guardians of all the children included in the study and written assent was obtained for children 8 years of age and above.

Based on the provided information, here are some potential innovations that could improve access to maternal health:

1. Mobile health clinics: Implementing mobile health clinics that can travel to remote areas and provide maternal health services, including prenatal care, vaccinations, and health education.

2. Telemedicine: Using telecommunication technology to provide remote consultations and medical advice to pregnant women in areas with limited access to healthcare facilities.

3. Community health workers: Training and deploying community health workers who can provide basic maternal health services, educate women about pregnancy and childbirth, and refer them to healthcare facilities when necessary.

4. Maternal health vouchers: Introducing voucher programs that provide pregnant women with access to essential maternal health services, such as prenatal care, delivery, and postnatal care.

5. Maternal health awareness campaigns: Conducting targeted awareness campaigns to educate women and their families about the importance of maternal health, the available services, and how to access them.

6. Improving transportation infrastructure: Investing in transportation infrastructure, such as roads and ambulances, to ensure that pregnant women can reach healthcare facilities quickly and safely.

7. Strengthening healthcare facilities: Upgrading and equipping healthcare facilities in underserved areas to provide comprehensive maternal health services, including skilled birth attendance and emergency obstetric care.

8. Integrating maternal health services with other healthcare programs: Integrating maternal health services with existing healthcare programs, such as immunization campaigns or HIV/AIDS prevention and treatment programs, to reach more women and improve overall health outcomes.

9. Public-private partnerships: Collaborating with private sector organizations to expand access to maternal health services, leveraging their resources and expertise to reach more women in need.

10. Empowering women and girls: Promoting gender equality, education, and economic empowerment for women and girls, which can have a positive impact on maternal health outcomes by reducing early marriages, improving access to education, and increasing women’s decision-making power regarding their own health.
AI Innovations Description
Based on the information provided, the recommendation to improve access to maternal health is to implement interventions aimed at reducing the prevalence of asymptomatic parasitemia in high malaria transmission settings. This can include:

1. Mass distribution of insecticide-treated nets (ITNs): ITNs have been shown to be effective in reducing malaria transmission and protecting individuals from mosquito bites. A community-based free ITN distribution campaign, similar to the one conducted in Tororo District, can be implemented to ensure that pregnant women and their families have access to ITNs.

2. Intermittent preventive treatment (IPT) during pregnancy: IPT with antimalarial drugs, such as sulfadoxine-pyrimethamine, has been recommended by the World Health Organization for pregnant women in areas with moderate to high malaria transmission. This intervention can be integrated into antenatal care services to ensure that pregnant women receive the necessary treatment to prevent malaria and its adverse effects on maternal and child health.

3. Malaria case management: Prompt diagnosis and treatment of malaria cases is essential to prevent severe complications and reduce transmission. Health facilities should be equipped with diagnostic tools, such as rapid diagnostic tests, and appropriate antimalarial drugs to ensure that pregnant women and other individuals with malaria receive timely and effective treatment.

4. Health education and awareness: Community engagement and health education programs can play a crucial role in raising awareness about the importance of malaria prevention and control measures, including the use of ITNs, IPT during pregnancy, and seeking early treatment for malaria symptoms. These programs can be conducted through schools, community gatherings, and other platforms to reach a wide audience.

5. Collaboration and coordination: Effective implementation of interventions to improve access to maternal health requires collaboration and coordination among various stakeholders, including government agencies, healthcare providers, community leaders, and non-governmental organizations. A multi-sectoral approach can help ensure that resources are allocated efficiently and interventions are implemented in a coordinated manner.

By implementing these recommendations, it is expected that access to maternal health will be improved, leading to a reduction in the prevalence of asymptomatic parasitemia and its adverse effects on maternal and child health outcomes.
AI Innovations Methodology
To improve access to maternal health, here are some potential recommendations:

1. Mobile clinics: Implementing mobile clinics that can travel to remote areas and provide essential maternal health services such as prenatal care, vaccinations, and postnatal care.

2. Telemedicine: Utilizing telemedicine technology to connect pregnant women in remote areas with healthcare professionals who can provide virtual consultations and guidance.

3. Community health workers: Training and deploying community health workers who can provide basic maternal health services, education, and referrals in underserved areas.

4. Transportation support: Establishing transportation systems or subsidies to help pregnant women in remote areas access healthcare facilities for prenatal visits and delivery.

5. Maternal health education: Conducting community-based educational programs to raise awareness about the importance of maternal health and provide information on available services.

To simulate the impact of these recommendations on improving access to maternal health, a methodology could include the following steps:

1. Define the target population: Identify the specific population that will benefit from the recommendations, such as pregnant women in remote areas.

2. Collect baseline data: Gather data on the current access to maternal health services, including the number of pregnant women receiving care, distance to healthcare facilities, and any existing barriers.

3. Implement the recommendations: Introduce the recommended interventions, such as mobile clinics or community health workers, and track their implementation.

4. Monitor and evaluate: Continuously monitor the implementation of the recommendations and collect data on key indicators, such as the number of pregnant women reached, the frequency of prenatal visits, and the rate of complications during childbirth.

5. Analyze the data: Use statistical analysis techniques to analyze the collected data and assess the impact of the recommendations on improving access to maternal health. This could include comparing pre- and post-intervention data, conducting regression analyses, or calculating indicators such as the number of additional pregnant women reached.

6. Interpret the results: Interpret the findings to understand the effectiveness of the recommendations in improving access to maternal health. Identify any challenges or limitations encountered during the implementation process.

7. Adjust and refine: Based on the findings, make any necessary adjustments or refinements to the recommendations to further improve access to maternal health.

8. Repeat the process: Continuously repeat the monitoring and evaluation process to assess the long-term impact of the recommendations and make further improvements as needed.

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