A pilot study to determine the normal haematological indices for young Malawian adults in Blantyre, Malawi

Background Reference ranges for haematological and other laboratory tests in most African countries are based on populations in Europe and America and, because of environmental and genetic factors, these may not accurately reflect the normal reference ranges in African populations.Aim To determine the distribution of haematological parameters in healthy individuals residing in Blantyre, Malawi. We also examined the effect of sociodemographic and nutritional factors on the haematological variables.Methods We conducted a proof-of-concept cross-sectional study, involving 105 healthy blood donors at Malawi Blood Transfusion Service in Blantyre. Eligible participants were HIV-negative males and females, aged 19 to 35 years, who did not have any evidence of acute or chronic illness, or bloodborne infection. We performed the haematological tests at the Malawi- Liverpool Wellcome Trust laboratory in Blantyre, and the screening tests at Malawi Blood Transfusion Service laboratories.Results Out of 170 consenting healthy volunteers, haematological results were available for 105 participants. The proportions of results which were below the lower limit of the manufacturer’s reference ranges were 35.2% (37/105) for haemoglobin, 15.2% (16/105) for neutrophils, 23.8% (25/105) for eosinophils, and 88.6 % (93/105) for basophils. The proportions of results that were above the upper limit of the manufacturer’s reference ranges were 9.5% (10/105) for platelets and 12.4% (13/105) for monocytes. We also observed that the mean leucocyte and basophil counts were significantly higher in males than females (p = 0.042 and p = 0.015, respectively). There were no statistically significant differences in haematological results observed among different ethnic, age, and body mass index groups.Conclusions Over half of otherwise healthy study participants had at least one abnormal haematological result, using previously established foreign standards. More detailed studies are needed to establish locally relevant normal ranges for different age groups and other demographic characteristics of the Malawian population. This will lead to accurate interpretation of laboratory results

Model choices to obtain adjusted risk difference estimates from a binomial regression model with convergence problems: an assessment of methods of adjusted risk difference estimation

Background: Risk Difference (RD) is becoming the measure of choice for estimating effect size in antimalarial drug efficacy trials. Calculating RD using binomial regression is prone to model nonconvergence. Cheung's modified ordinary least squares (OLS) method is a proven technique for handling non-convergence when estimating RD. Other promising methods include the Poison, Additive Binomial Regression and binary regression models fitted using the statistical package R. (Deddens') Copy method that was primarily developed to overcome non-convergence of log-binomial regression models when estimating risk ratios is another potential method. Simulations were conducted to compare the performance of the Copy method against four alternatives (Cheung's modified OLS method, the Additive Binomial Regression Model fitted with the blm algorithm, the binary regression model fitted with the glm2 algorithm, and the Poisson model with identity link and robust standard errors fitted with the glm algorithm) for obtaining RD estimates when a binomial model fails to converge. Methods: We computed estimates of efficiency and bias with treatment arm efficacies of (a) 60% vs. 85%, (b) 95% vs. 90%, (iii) 95% vs. 98% using simulation studies. A total of 5,000 datasets were simulated under each of these three scenarios. Results: The modified OLS method and the binary regression model fitted using the glm2 algorithm in R provided unbiased, efficient estimates of RD across all assessed scenarios. In contrast, the Copy method yielded biased estimates of RD even when 100% convergence was achieved. The Poisson and Additive Binomial Regression models had 100% and almost 100% convergence rates respectively, but both produced very slightly biased RD estimates. Conclusion: The Copy method is not suitable for estimating RD when binomial regression model fitting fails to converge. Cheung's modified OLS or the binary regression model fitted using the glm2 algorithm in R should be the method of choice to overcome non-convergence with binomial models for calculating adjusted RD estimates

Qualitative study to develop processes and tools for the assessment and tracking of African institutions’ capacity for operational health research

Objectives Research is key to achieving global development goals. Our objectives were to develop and test an evidence-informed process for assessing health research management and support systems (RMSS) in four African universities and for tracking interventions to address capacity gaps. Setting Four African universities. Participants 83 university staff and students from 11 cadres. Intervention/methods A literature-informed ‘benchmark’ was developed and used to itemise all components of a university’s health RMSS. Data on all components were collected during site visits to four African universities using interview guides, document reviews and facilities observation guides. Gaps in RMSS capacity were identified against the benchmark and institutional action plans developed to remedy gaps. Progress against indicators was tracked over 15 months and common challenges and successes identified. Results Common gaps in operational health research capacity included no accessible research strategy, a lack of research e-tracking capability and inadequate quality checks for proposal submissions and contracts. Feedback indicated that the capacity assessment was comprehensive and generated practical actions, several of which were no-cost. Regular follow-up helped to maintain focus on activities to strengthen health research capacity in the face of challenges. Conclusions Identification of each institutions’ strengths and weaknesses against an evidence-informed benchmark enabled them to identify gaps in in their operational health research systems, to develop prioritised action plans, to justify resource requests to fulfil the plans and to track progress in strengthening RMSS. Use of a standard benchmark, approach and tools enabled comparisons across institutions which has accelerated production of evidence about the science of research capacity strengthening. The tools could be used by institutions seeking to understand their strengths and to address gaps in research capacity. Research capacity gaps that were common to several institutions could be a ‘smart’ investment for governments and health research funders

Provider and user acceptability of intermittent screening and treatment for the control of malaria in pregnancy in Malawi.

BACKGROUND: Malaria in pregnancy is a major cause of adverse maternal and fetal outcomes. Intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) is one of the control strategies promoted by WHO. In response to mounting resistance to SP, intermittent screening and treatment (ISTp) has been proposed as an alternative. The objective of this study was to explore the acceptability of ISTp for health workers and pregnant women. METHODS: Semi-structured interviews of ten health workers and five focus group discussions of 38 women enrolled in an ongoing trial comparing IPTp-SP and ISTp with dihydroartemisinin-piperaquine (DP) were conducted at two antenatal clinics in rural Malawi. All transcripts were coded and themes were identified using a content analysis approach. RESULTS: Amongst health workers, there were contrasting opinions on the preference of blood sampling methods, and the influence of method on reliability of diagnosis. The perceived greater effectiveness of DP compared to SP was appreciated, however concerns of user compliance with the full dose of DP in non-trial settings were raised. Despite the discomfort of repeated finger pricks, pregnant women were generally accepting of ISTp, particularly the chance for regular blood tests to check for infections and the perceived greater effectiveness with fewer side effects of DP compared to SP. CONCLUSION: In the trial context, pregnant women tended to prefer ISTp-DP over IPTp-SP. Health workers were also accepting of ISTp-DP as an alternative to IPTp-SP in light of increasing SP resistance. However, reliability of stock, adherence to malaria test results and user adherence to the full course of DP may present barriers to successful routine implementation. Effective communication with health workers and between health workers, pregnant women and their communities will be essential for the acceptability of focused antenatal care, including the best malaria control measures available

Curtailing COVID-19 on a Dollar-a-Day in Malawi: Implications for the Ongoing Pandemic

Utilizing population-based data from the COVID-19 phone survey (N=2,262$) of the Malawi Longitudinal Study of Families and Health (MLSFH) collected during June 2nd--August 17th, 2020, we investigate behavioral, economic and social responses COVID-19 and focus on the crucial role that community leadership and trust in institutions play towards shaping these responses. We argue that the effective response of Malawi to limit the spread of the virus was facilitated by the engagement of local leaders to mobilize communities to adapt and adhere to COVID-19 prevention strategies. Village heads (VHs) played pivotal role in shaping individual\u27s knowledge about the pandemic and the adaption of preventive health behaviors and were crucial for mitigating the negative economic and health consequences of the pandemic. We further show that trust in institutions is of particular importance in shaping individuals\u27 behavior during the pandemic, and these findings highlight the pivotal role of community leadership in fostering better compliance and adoption of public health measures essential to contain the virus. Overall, our findings point to distinctive patterns of pandemic response in a low-income sub-Saharan African rural population that emphasized local leadership as mediators of public health messages and policies. These lessons from the first pandemic wave remain relevant as in many low-income countries behavioral responses to COVID-19 will remain the primary prevention strategy for a foreseeable future

Qualitative study to develop processes and tools for the assessment and tracking of African institutions’ capacity for operational health research

Objectives Research is key to achieving global development goals. Our objectives were to develop and test an evidence-informed process for assessing health research management and support systems (RMSS) in four African universities and for tracking interventions to address capacity gaps. Setting Four African universities. Participants 83 university staff and students from 11 cadres. Intervention/methods A literature-informed ‘benchmark’ was developed and used to itemise all components of a university’s health RMSS. Data on all components were collected during site visits to four African universities using interview guides, document reviews and facilities observation guides. Gaps in RMSS capacity were identified against the benchmark and institutional action plans developed to remedy gaps. Progress against indicators was tracked over 15 months and common challenges and successes identified. Results Common gaps in operational health research capacity included no accessible research strategy, a lack of research e-tracking capability and inadequate quality checks for proposal submissions and contracts. Feedback indicated that the capacity assessment was comprehensive and generated practical actions, several of which were no-cost. Regular follow-up helped to maintain focus on activities to strengthen health research capacity in the face of challenges. Conclusions Identification of each institutions’ strengths and weaknesses against an evidence-informed benchmark enabled them to identify gaps in in their operational health research systems, to develop prioritised action plans, to justify resource requests to fulfil the plans and to track progress in strengthening RMSS. Use of a standard benchmark, approach and tools enabled comparisons across institutions which has accelerated production of evidence about the science of research capacity strengthening. The tools could be used by institutions seeking to understand their strengths and to address gaps in research capacity. Research capacity gaps that were common to several institutions could be a ‘smart’ investment for governments and health research funders

Hygiene in early childhood development centres in low-income areas of Blantyre, Malawi

Diarrhoeal disease remains a leading cause of death in children in sub-Saharan Africa, attributed to environmental health factors such as inadequate water, sanitation and hygiene (WASH) and food hygiene. This formative study in low-income areas of Blantyre focussed on the practices in Early Childhood Development Centre (ECDCs) environments where children spend a significant amount of time. A mixed-methods approach was applied to identify key hygiene behaviours in ECDCs through; checklist and structured observations (n = 849 children; n = 33 caregivers), focus group discussions (n = 25) and microbiological sampling (n = 261) of drinking water, food handler’s hands, and eating utensils. ECDCs had inadequate WASH infrastructure; coupled with poor hygiene practices and unhygienic environments increased the risk of faecal-oral disease transmission. Presence of E. coli in drinking water confirmed observed poor water handling habits by staff and children. Addressing undesired hygiene practices in ECDCs has the potential to improve the health outcomes of children in low-income settings

From ‘intuitive’ pragmatic interventions to a systematic approach – Using implementation science to improve childhood cancer survival in low-income settings: The CANCaRe Africa experience

Implementation science is a relatively young field of study and is the science of delivering evidence-based interventions into routine health care. RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) is an evaluation-type implementation science framework. CANCaRe Africa is preparing a project to assess the implementation and effectiveness of a cash incentive intervention to support families with out-of-pocket costs to prevent treatment abandonment and increase childhood cancer survival in sub-Saharan Africa. Our strategy is to enhance the dissemination of our research findings to local policymakers who can support the scale-up of evidence-based clinical interventions and locally effective implementation strategies. It can be done best by embedding implementation science into our clinical research approaches

A whole genome association study of mother-to-child transmission of HIV in Malawi

Abstract: Background: More than 300,000 children are newly infected with HIV each year, predominantly through mother-to-child transmission (HIV MTCT). Identification of host genetic traits associated with transmission may more clearly explain the mechanisms of HIV MTCT and further the development of a vaccine to protect infants from infection. Associations between transmission and a selection of genes or single nucleotide polymorphisms (SNP)s may give an incomplete picture of HIV MTCT etiology. Thus, this study employed a genome-wide association approach to identify novel variants associated with HIV MTCT. Methods: We conducted a nested case-control study of HIV MTCT using infants of HIV(+) mothers, drawn from a cohort study of malaria and HIV in pregnancy in Blantyre, Malawi. Whole genome scans (650,000 SNPs genotyped using Illumina genotyping assays) were obtained for each infant. Logistic regression was used to evaluate the association between each SNP and HIV MTCT. Results: Genotype results were available for 100 HIV(+) infants (at birth, 6, or 12 weeks) and 126 HIV(-) infants (at birth, 6, and 12 weeks). We identified 9 SNPs within 6 genes with a P-value <5 × 10-5 associated with the risk of transmission, in either unadjusted or adjusted by maternal HIV viral load analyses. Carriers of the rs8069770 variant allele were associated with a lower risk of HIV MTCT (odds ratio = 0.27, 95% confidence interval = 0.14, 0.51), where rs8069770 is located within HS3ST3A1, a gene involved in heparan sulfate biosynthesis. Interesting associations for SNPs located within or near genes involved in pregnancy and development, innate immunological response, or HIV protein interactions were also observed. Conclusions: This study used a genome-wide approach to identify novel variants associated with the risk of HIV MTCT in order to gain new insights into HIV MTCT etiology. Replication of this work using a larger sample size will help us to differentiate true positive findings

Correction: A whole genome association study of mother-to-child transmission of HIV in Malawi

A correction to: Bonnie R Joubert, Ethan M Lange, Nora Franceschini, Victor Mwapasa, Kari E North, Steven R Meshnick andthe NIAID Center for HIV/AIDS Vaccine Immunology. A whole genome association study of mother-to-child transmission of HIV in Malawi. Genome Medicine 2010, 2:17