Developmental Origins of Health and Disease: the relevance to developing nations.

Low- and middle-income countries (LMICs), particularly those in sub-Saharan Africa, are experiencing rapid increases in the prevalence of non-communicable diseases (NCDs), which may not be fully explained by urbanization and associated traditional risk factors such as tobacco smoking, excessive alcohol consumption, poor diet or physical inactivity. In this commentary, we draw attention to the concept of Developmental Origins of Health and Disease (DOHaD), where environmental insults in early life can contribute to long-term risk of NCDs, the impact of which would be particularly important in LMICs where poverty, malnutrition, poor sanitation and infections are still prevalent

AcSDKP is down-regulated in anaemia induced by Trypanosoma brucei infection in mice

Background Anaemia commonly results from destruction of erythrocytes in the peripheral blood and failure of the bone marrow haematopoietic cells to replenish the erythrocytes. The mechanisms involved in trypanosoma-induced anaemia, including the role of the bone marrow haematopoietic cells are incompletely understood. We studied the responses of a tetrapeptide, AcSDKP, and IL-10, and their association with bone marrow nucleated cells in a Trypanosoma brucei brucei GVR35 experimental infection model.Methods Mouse infection was done intraperitoneally with 1 × 103 trypanosomes/mL. Mice were either infected or left uninfected (N = 100). At days 0, 9, 16, 23, 30, 37, and 44 post-infection, mice were euthanised and blood was collected by cardiac puncture to examine for parasitaemia and packed cell volume (PCV) and then centrifuged for plasma, which was used for cytokine ELISA. The mice’s femurs were also dissected and bone marrow was collected for femur cellularity.Results PCV dropped from 39.6% to 27% in infected animals by day 9 and remained low (relative to uninfected mice) for the duration of the experiment. AcSDKP levels decreased from day 0 (11.5 × 104 pg/mL) to day 16 (10 × 104), and increased by day 30 (12.6 × 104). There was a significant difference at day 16 (P = 0.023) between the infected and uninfected groups. By contrast, expression of IL-10 markedly increased between day 0 (18.6 pg/mL) and day 16 (145 pg/mL) and decreased by day 30 (42.8 pg/mL). There was also a significant difference in IL-10 expression between infected and uninfected mice at day 16 (P < 0.001). Bone marrow nucleated cells were significantly reduced during periods of low plasma AcSDKP and high plasma IL-10 concentrations (5.4 × 106 infected vs 6.2 × 106 on day 0 and 4.9 × 106 infected vs 10 × 106 uninfected on day 16).Conclusions These data unravel a possible negative feedback interaction between AcSDKP and IL-10 in trypanosome infection. More importantly, this study implicates an IL-10/AcSDKP cytokine network in the regulation of bone marrow nucleated cells and provides a new potential mechanism in the pathogenesis of trypanosoma-induced anaemia. Further mechanistic blocking experiments on AcSDKP and IL-10 are recommended to further clarify understanding of the interaction

Apparent Insulin Deficiency in an Adult African Population With New-Onset Type 2 Diabetes

Identifying patients with new-onset type 2 diabetes who have insulin deficiency can aid in timely insulin replacement therapy. In this study, we measured fasting C-peptide concentration to assess endogenous insulin secretion and determine the prevalence and characteristics of patients with insulin deficiency in adult Ugandan patients with confirmed type 2 diabetes at presentation.MethodsAdult patients with new-onset diabetes were recruited from seven tertiary hospitals in Uganda. Participants who were positive for the three islet autoantibodies were excluded. Fasting C-peptide concentrations were measured in 494 adult patients, and insulin deficiency was defined as a fasting C-peptide concentration <0.76 ng/ml. The socio-demographic, clinical, and metabolic characteristics of participants with and without insulin deficiency were compared. Multivariate analysis was performed to identify independent predictors of insulin deficiency.ResultsThe median (IQR) age, glycated haemoglobin (HbA1c), and fasting C-peptide of the participants was 48 (39-58) years,10.4 (7.7-12.5) % or 90 (61-113) mmol/mol, and 1.4 (0.8-2.1) ng/ml, respectively. Insulin deficiency was present in 108 (21.9%) participants. Participants with confirmed insulin deficiency were more likely to be male (53.7% vs 40.4%, p=0.01), and had a lower body mass index or BMI [p<0.001], were less likely to be hypertensive [p=0.03], had reduced levels of triglycerides, uric acid, and leptin concentrations [p<0.001]), but higher HbA1c concentration (p=0.004). On multivariate analysis, BMI (AOR 0.89, 95% CI 0.85-0.94, p<0.001), non-HDLC (AOR 0.77, 95% CI 0.61-0.97, p=0.026), and HbA1c concentrations (AOR 1.08, 95% CI 1.00-1.17, p=0.049) were independent predictors of insulin deficiency.ConclusionInsulin deficiency was prevalent in this population, occurring in about 1 in every 5 patients. Participants with insulin deficiency were more likely to have high HbA1c and fewer markers of adiposity and metabolic syndrome. These features should increase suspicion of insulin deficiency and guide targeted testing and insulin replacement therapy

Prevalence and risk factors for anemia severity and type in Malawian men and women: urban and rural differences.

BACKGROUND: The global burden of anemia is large especially in sub-Saharan Africa, where HIV is common and lifestyles are changing rapidly with urbanization. The effects of these changes are unknown. Studies of anemia usually focus on pregnant women or children, among whom the burden is greatest. We describe prevalence and risk factors for anemia among rural and urban men and women of all ages in Malawi. METHODS: We analyzed data from a population-wide cross-sectional survey of adults conducted in two sites, Karonga (rural) and Lilongwe (urban), commencing in May 2013. We used multinomial logistic regression models, stratified by sex to identify risk factors for mild and moderate-to-severe anemia. RESULTS: Anemia prevalence was assessed among 8,926 men (age range 18-100 years) and 14,978 women (age range: 18-103 years). Weighted prevalence levels for all, mild, and moderate-to-severe anemia were 8.2, 6.7 and 1.2% in rural men; 19.4, 12.0 and 7.4% in rural women; 5.9, 5.1 and 0.8% in urban men; and 23.4, 13.6 and 10.1% in urban women. Among women, the odds of anemia were higher among urban residents and those with higher socioeconomic status. Increasing age was associated with higher anemia prevalence in men. Among both men and women, HIV infection was a consistent risk factor for severity of anemia, though its relative effect was stronger on moderate-to-severe anemia. CONCLUSIONS: The drivers of anemia in this population are complex, include both socioeconomic and biological factors and are affecting men and women differently. The associations with urban lifestyle and HIV indicate opportunities for targeted intervention

Non-communicable Lung Disease in Sub Saharan Africa: a Community-based Cross-sectional Study of Adults in Urban Malawi

Rationale Non-communicable diseases (NCD) are major causes of morbidity and mortality in sub-Saharan Africa (sSA). Valid burden of disease estimates are lacking for non-communicable lung disease in sSA. Objectives We performed a community-based survey to determine the prevalence of chronic lung disease amongst adults ≥18 years in Malawi, using ATS standard spirometry, internationally validated respiratory symptom and exposure questionnaires, and including assessment of HIV-status. Methods An age and gender stratified random sample of 2000 adults was taken from the population of Chilomoni district of Blantyre, Malawi. Fieldworkers collected questionnaire data, conducted HIV-testing and performed pre/post bronchodilator spirometry on eligible participants. Survey-weighted population prevalence estimates of respiratory symptoms and spirometric abnormalities were computed, and bivariate and multivariable regression were used to identify associated variables. Results Questionnaire data, HIV status and BOLD standard spirometry were obtained from 1059, 937 and 749 participants respectively. Current respiratory symptoms, exposure to biomass and ever smoking were reported by 11.8%, 85.2% and 10.4% respectively. HIV prevalence was 24.2%. Moderate-severe airway obstruction was seen in 3.6%. The prevalence of spirometric restriction was 38.6% using NHANES reference ranges and 9.0% using local reference ranges. Age was positively associated with obstruction while low BMI was associated with restriction. Conclusions Over 40% of the Malawian adults in our urban population-representative sample had abnormal lung function (mostly restrictive) in the context of widespread exposure to biomass smoke and high HIV prevalence. These findings have potentially major pubic health implications for Malawi and the broader sSA region

Prevalence of impaired renal function among rural and urban populations: findings of a cross-sectional study in Malawi

Background: Sub-Saharan Africa faces region-specific risk factors for chronic kidney disease (CKD), such as nephrotoxic herbal medicines, antiretroviral therapy and infections, in addition to hypertension and diabetes. However, large epidemiological studies from this area are scarce. Methods: In a cross-sectional survey of non-communicable diseases, we conducted a prevalence sub-study of CKD in two Malawian populations. Study participants (N=5264) of 18 years of age and above were recruited and data on demographics and CKD risk factors were collected. Glomerular filtration rate was estimated (eGFR) using the CKD-EPI equation. Results: The prevalence of eGFR<60ml/min/1.73m2 was 1.4% (95% CI 1.1 – 1.7%) and eGFR<90ml/min/1.73m2 was 20.6% (95% CI 19.5 – 21.7%). The rural area had higher age-standardized prevalence of both eGFR<60ml/min/1.73m2, at 1.8% (95% CI 1.4 – 2.3) and eGFR <90 ml/min/1.73m², at 21.1% (95% CI 19.9 – 22.3), than urban location, which had a prevalence of 1.5%, (95% CI 1.0 – 2.2) and 19.4% (95% CI 18.0 – 20.8), respectively, with overlapping confidence intervals. The prevalence of CKD was lower in females than in males in both rural and urban areas. Older age (p < 0.001), a higher level of education (p = 0.03) and hypertension (p < 0.001) were associated with a higher adjusted odds ratio (aOR) of low eGFR. Diabetes was associated with a reduced aOR of eGFR<90ml/min/1.73m2 of 0.69 (95% CI 0.49–0.96; p=0.03). Of participants with eGFR<60ml/min/1.73m2, 14 (19.4%) had no history of hypertension, diabetes or HIV, while 36 (50%) had a single risk factor of being hypertensive. Conclusions: Impaired renal function is prevalent, but lower than expected, in rural and urban Malawi. Further research is needed to increase understanding of CKD incidence, survival and validation of eGFR calculations in this population

Apparent Insulin Deficiency in an Adult African Population With New-Onset Type 2 Diabetes

Identifying patients with new-onset type 2 diabetes who have insulin deficiency can aid in timely insulin replacement therapy. In this study, we measured fasting C-peptide concentration to assess endogenous insulin secretion and determine the prevalence and characteristics of patients with insulin deficiency in adult Ugandan patients with confirmed type 2 diabetes at presentation. METHODS: Adult patients with new-onset diabetes were recruited from seven tertiary hospitals in Uganda. Participants who were positive for the three islet autoantibodies were excluded. Fasting C-peptide concentrations were measured in 494 adult patients, and insulin deficiency was defined as a fasting C-peptide concentration <0.76 ng/ml. The socio-demographic, clinical, and metabolic characteristics of participants with and without insulin deficiency were compared. Multivariate analysis was performed to identify independent predictors of insulin deficiency. RESULTS: The median (IQR) age, glycated haemoglobin (HbA1c), and fasting C-peptide of the participants was 48 (39-58) years,10.4 (7.7-12.5) % or 90 (61-113) mmol/mol, and 1.4 (0.8-2.1) ng/ml, respectively. Insulin deficiency was present in 108 (21.9%) participants. Participants with confirmed insulin deficiency were more likely to be male (53.7% vs 40.4%, p=0.01), and had a lower body mass index or BMI [p<0.001], were less likely to be hypertensive [p=0.03], had reduced levels of triglycerides, uric acid, and leptin concentrations [p<0.001]), but higher HbA1c concentration (p=0.004). On multivariate analysis, BMI (AOR 0.89, 95% CI 0.85-0.94, p<0.001), non-HDLC (AOR 0.77, 95% CI 0.61-0.97, p=0.026), and HbA1c concentrations (AOR 1.08, 95% CI 1.00-1.17, p=0.049) were independent predictors of insulin deficiency. CONCLUSION: Insulin deficiency was prevalent in this population, occurring in about 1 in every 5 patients. Participants with insulin deficiency were more likely to have high HbA1c and fewer markers of adiposity and metabolic syndrome. These features should increase suspicion of insulin deficiency and guide targeted testing and insulin replacement therapy

Diagnosis of gestational diabetes in Uganda: The reactions of women, family members and health workers.

OBJECTIVES: In Uganda, as in many other low- and middle-income countries, screening for gestational diabetes mellitus is suboptimal and is rarely embedded in routine antenatal care. We describe the experiences of women in Uganda who underwent screening for gestational diabetes mellitus and were diagnosed with the condition as they navigate both the reaction of family members and their interaction with health workers. METHODS: Pregnant women aged 18 years or older and between 24 and 28 weeks of gestation were enrolled from the antenatal clinics at one of the five hospitals between 13 June 2018 and 31 October 2019. Ten women with gestational diabetes mellitus, ten family members and six health workers were purposively selected to take part. Interviews and focus group discussions were used to collect data on the socio-cultural and health system factors that influence timely screening and effective management of gestational diabetes mellitus in Uganda. Data were analysed thematically. RESULTS: Women generally reflected on the importance of gestational diabetes mellitus screening and felt that an early diagnosis helped them to get timely medical attention, and most reported a positive experience of the care provided by health workers. However, women who were diagnosed with gestational diabetes mellitus reported feeling fearful and anxious, and some were worried that the condition might be life-threatening. Many women reported that they were upset and largely unprepared to receive a gestational diabetes mellitus diagnosis. A gestational diabetes mellitus diagnosis not only stirred intense feelings of fear and anxiety in women but also affected their spouses and other family members. Many male partners were sympathetic and willing to provide support. CONCLUSION: Our findings highlight the need to understand the perceptions and emotions that accompany a gestational diabetes mellitus diagnosis to best support women and their family members. An improved recognition of these factors can inform the development of effective gestational diabetes mellitus screening and management programmes