How do women prepare for pregnancy in a low-income setting? Prevalence and associated factors

Background Despite growing evidence of pregnancy preparation benefits, there is little knowledge on how women in developing countries prepare for pregnancy and factors influencing their preparedness for pregnancy. Here, we determine how women in Malawi prepare for pregnancy and factors associated with pregnancy preparation. Methods We used data from a previous cohort study comprising 4,244 pregnant mothers, recruited between March and December 2013 in Mchinji district, Malawi. Associations of pregnancy preparation with socio-demographic and obstetric factors were tested for using mixed effects ordinal regression, with the likelihood ratio and Wald's tests used for variable selection and independently testing the associations. Results Most mothers (63.9%) did not take any action to prepare for their pregnancies. For those who did (36.1%), eating more healthily (71.9%) and saving money (42.8%) were the most common forms of preparation. Mothers who were married (adjusted odds-ratio (AOR 7.77 (95% CI [5.31, 11.25]) or with no or fewer living children were more likely to prepare for pregnancy (AOR 4.71, 95% CI [2.89,7.61]. Mothers with a period of two to three years (AOR 2.51, 95% CI [1.47, 4.22]) or at least three years (AOR 3.67, 95%CI [2.18, 6.23]) between pregnancies were more likely to prepare for pregnancy than women with first pregnancy or shorter intervals. On the other hand, teenage and older (≥ 35 years old) mothers were less likely to prepare for pregnancy (AOR 0.61, 95%CI [0.47, 0.80]) and AOR 0.49 95%CI [0.33, 0.73], respectively). Conclusion While preconception care may not be formally available in Malawi, our study has revealed that over a third of mothers took some action to prepare for pregnancy before conception. Although this leaves around two thirds of women who did not make any form of pregnancy preparation, our findings form a basis for future research and development of a preconception care package that suits the Malawian context

Epidemiological and genomic landscape of antimicrobial resistance in Malawi

Antimicrobial resistance (AMR) is a global public health problem, which presents a huge threat to the treatment of all forms of bacterial infections. A wide range of bacterial pathogens across the globe are increasingly developing resistance to multiple classes of antimicrobial agents rendering the agents concerned ineffective for the treatment of infections. Bloodstream infection (BSI) and other bacterial infections in sub-Saharan Africa (SSA) and Malawi in particular, are a common cause of morbidity and mortality. Few facilities in SSA however, are able to conduct long-term surveillance and as such the full burden of drug resistant infection (DRI) remain largely unknown across the region. In this thesis, blood cultures routinely taken from adult and paediatric medical patients admitted to Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi between 1998 and 2016 were analysed to describe trends in BSI and AMR. The analysis revealed a significant decline of BSI in all major pathogens except S. Typhi. However, the majority of isolates were resistant to the Malawian first-line antimicrobial agents (ampicillin, cotrimoxazole and chloramphenicol). Resistance to all the first line antimicrobial agents was more common in Gram-negative pathogens than Gram-positive pathogens. Non-Salmonellae Enterobacteriaceae that produced extended spectrum beta-lactamase (ESBL) and were fluoroquinolone-resistant were detected, and the proportions of these isolates rose significantly during the surveillance. In contrast, a majority of common Gram-positive pathogens remain susceptible to either penicillin or chloramphenicol. Methicillin resistant S. aureus was first reported in 1998 but became regularly detected in the later years of the surveillance. The analysis of blood culture isolates identified E. coli as one of the common causes of BSI in Blantyre, and the proportion of these isolates that were ESBL producers increased over time. Globally, efforts to treat E. coli infections are increasingly being compromised by the rapid, global spread of ESBL-producing E. coli. In this thesis, a whole genome sequencing (WGS) study was carried out to investigate the genetic population structure and molecular determinants of AMR in E. coli isolates from Malawi. Whole genomes of clinical E. coli isolates from patients admitted to QECH were sequenced and analysed using phylogenetic methods and comparative genomics. It was revealed that the E. coli population in Malawi is highly diverse with isolates belonging to five phylogroups, corresponding to five isolate sequence clusters (SCs) that contained over forty sequence types (STs). A unique sub-lineage of ST131 was identified that was distinct from previously defined sub-lineages of this globally disseminated ST. The most common ESBL gene was blaCT X-M-15. Unlike in other settings where presence of the blaCT X-M-15 gene was strongly linked to ST131, here the gene was not lineage-specific suggesting a distinct genomic landscape of ESBL-producing E. coli in Malawi. This thesis also identified Klebsiella spp. isolates as a common cause of BSI in Blantyre, and an increasing proportion of ESBL-producing and fluoroquinolone resistant isolates were identified. The molecular mechanisms and clones of K. pneumoniae associated with ESBL production and fluoroquinolone resistance were yet to be explored in Malawi. Here, a number of K. pneumoniae isolates were selected for WGS, and placed in a global context by comparison with previously sequenced K. pneumoniae isolates from multiple locations outside SSA, in order to identify the molecular determinants of AMR and determine their relationship with K. pneumoniae population structure. Genomic analysis revealed three main lineages of K. pneumoniae, which corresponded to the previously defined KpI, KpII and KpIII lineages. All three lineages exhibited high genetic diversity. Further phylogenetic analysis revealed a sub-lineage of KpI to be a major cause of CA infections in Malawi. The sub-lineage included the clonally related ST14 and ST15 of K. pneumoniae which cause hospital acquired infection in multiple settings across the globe, A large pool of AMR genes, was identified in the genomes of the Malawian isolates, including multiple ESBL and qnr genes. Plasmid-encoded CTX-M-15 was the most common type of ESBL that was identified. In common with E. coli from Malawi, AMR was not restricted to a particular clade of K. pneumoniae. These findings suggest that dissemination of AMR in the K. pneumoniae population in Malawi was either due to a combination of horizontal gene transfer and clonal expansion, or horizontal gene transfer alone. In conclusion, the thesis has shown that ESBL production and fluoroquinolone resistance is rapidly spreading in Malawi across multiple E. coli and K. pneumoniae lineages that are causing increasing levels of infection. As cephalosporins and fluoroquinolones remain the last resort antimicrobial agents in this setting, urgent action is needed to curb the spread of Gram-negative AMR pathogens

Genomic analysis of Klebsiella pneumoniae isolates from Malawi reveals acquisition of multiple ESBL determinants across diverse lineages

Objectives ESBL-producing Klebsiella pneumoniae (KPN) pose a major threat to human health globally. We carried out a WGS study to understand the genetic background of ESBL-producing KPN in Malawi and place them in the context of other global isolates. Methods We sequenced genomes of 72 invasive and carriage KPN isolates collected from patients admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi. We performed phylogenetic and population structure analyses on these and previously published genomes from Kenya (n = 66) and from outside sub-Saharan Africa (n = 67). We screened for presence of antimicrobial resistance (AMR) genetic determinants and carried out association analyses by genomic sequence cluster, AMR phenotype and time. Results Malawian isolates fit within the global population structure of KPN, clustering into the major lineages of KpI, KpII and KpIII. KpI isolates from Malawi were more related to those from Kenya, with both collections exhibiting more clonality than isolates from the rest of the world. We identified multiple ESBL genes, including blaCTX-M-15, several blaSHV, blaTEM-63 and blaOXA-10, and other AMR genes, across diverse lineages of the KPN isolates from Malawi. No carbapenem resistance genes were detected; however, we detected IncFII and IncFIB plasmids that were similar to the carbapenem resistance-associated plasmid pNDM-mar. Conclusions There are multiple ESBL genes across diverse KPN lineages in Malawi and plasmids in circulation that are capable of carrying carbapenem resistance. Unless appropriate interventions are rapidly put in place, these may lead to a high burden of locally untreatable infection in vulnerable populations

Household acquisition and transmission of extended-spectrum β-lactamase (ESBL) -producing Enterobacteriaceae after hospital discharge of ESBL-positive index patients

Objectives: This study aimed to determine rates and risk factors of extended-spectrum b-lactamaseproducing Enterobacteriaceae (ESBL-PE) acquisition and transmission within households after hospital discharge of an ESBL-PE-positive index patient. Methods: Two-year prospective cohort study in five European cities. Patients colonized with ESBLproducing Escherichia coli (ESBL-Ec) or Klebsiella pneumoniae (ESBL-Kp), and their household contacts were followed up for 4 months after hospital discharge of the index case. At each follow up, participants provided a faecal sample and personal information. ESBL-PE whole-genome sequences were compared using pairwise single nucleotide polymorphism-based analysis. Results: We enrolled 71 index patients carrying ESBL-Ec (n ¼ 45), ESBL-Kp (n ¼ 20) or both (n ¼ 6), and 102 household contacts. The incidence of any ESBL-PE acquisition among household members initially free of ESBL-PE was 1.9/100 participant-weeks at risk. Nineteen clonally related household transmissions occurred (case to contact: 13; contact to case: 6), with an overall rate of 1.18 transmissions/100 participant-weeks at risk. Most of the acquisition and transmission events occurred within the first 2 months after discharge. The rate of ESBL-Kp household transmission (1.16/100 participant-weeks) was higher than of ESBL-Ec (0.93/100 participant-weeks), whereas more acquisitions were noted for ESBL-Ec (1.06/100 participant-weeks) compared with ESBL-Kp (0.65/100 participant-weeks). Providing assistance for urinary and faecal excretion to the index case by household members increased the risk of ESBL-PE transmission (adjusted prevalence ratio 4.3; 95% CI 1.3e14.1).Instituto de Salud Carlos II

How does the association of general and central adiposity with glycaemia and blood pressure differ by gender and area of residence in a Malawian population: a cross-sectional study.

BACKGROUND: In high-income settings, body mass index (BMI) and measures of central adiposity, such as waist-to-hip ratio (WHR) are associated with cardiometabolic risk, but evidence from low-income settings, particularly sub-Saharan Africa (SSA), is limited. We assessed whether there are differences between central and general adiposity in their associations with fasting glucose, diabetes, systolic and diastolic blood pressures and hypertension, and whether these associations differ with gender or rural/urban setting in Malawi. METHODS: We used data from a population-based study of 27 880 Malawian adults aged  ≥18 years, from both rural and urban areas. We used age-standardized z-scores of the means of BMI and WHR to directly compare their associations with glycaemic and blood pressure outcomes. RESULTS: Mean fasting glucose and blood pressure values and odds of hypertension increased linearly across fifths of BMI and WHR, with stronger associations with BMI. For both BMI and WHR, the associations with outcomes were stronger in urban versus rural residents. The association with diabetes was stronger in women than men, whereas for blood-pressure related outcomes a stronger association was seen in men. CONCLUSIONS: BMI is more strongly associated with cardiometabolic risk in SSA, and might be a more useful measure than WHR, in this population. The greater positive association of adiposity with cardiometabolic outcomes in urban residents (where rates of overweight/obesity are already high) highlights the particular importance of addressing obesity within urban SSA populations

Glycated haemoglobin A1c (HbA1c) for detection of diabetes mellitus and impaired fasting glucose in Malawi: a diagnostic accuracy study.

OBJECTIVES: To examine the accuracy of glycated haemoglobin A1c (HbA1c) in detecting type 2 diabetes and impaired fasting glucose among adults living in Malawi. DESIGN: A diagnostic validation study of HbA1c. Fasting plasma glucose (FPG) ≥7.0 mmol/L was the reference standard for type 2 diabetes, and FPG between 6.1 and 6.9 mmol/L as impaired fasting glucose. PARTICIPANTS: 3645 adults (of whom 63% were women) recruited from two demographic surveillance study sites in urban and rural Malawi. This analysis excluded those who had a previous diagnosis of diabetes or had history of taking diabetes medication. RESULTS: HbA1c demonstrated excellent validity to detect FPG-defined diabetes, with an area under the receiver operating characteristic (AUROC) curve of 0.92 (95% CI 0.90 to 0.94). At HbA1c ≥6.5% (140 mg/dL), sensitivity was 78.7% and specificity was 94.0%. Subgroup AUROCs ranged from 0.86 for participants with anaemia to 0.94 for participants in urban Malawi. There were clinical and metabolic differences between participants with true diabetes versus false positives when HbA1c was ≥6.5% (140 mg/dL). CONCLUSIONS: The findings from this study provide justification to use HbA1c to detect type 2 diabetes. As HbA1c testing is substantially less burdensome to patients than either FPG testing or oral glucose tolerance testing, it represents a useful option for expanding access to diabetes care in sub-Saharan Africa

Emerging resistance to empiric antimicrobial regimens for pediatric bloodstream infections in Malawi (1998-2017)

Background The adequacy of the WHO Integrated Management of Childhood Illness (IMCI) antimicrobial guidelines for the treatment of suspected severe bacterial infections is dependent on a low prevalence of antimicrobial resistance (AMR). We describe trends in etiologies and susceptibility patterns of bloodstream infections (BSI) in hospitalized children in Malawi. Methods We determined the change in population-based incidence of BSI in children admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi (1998-2017). AMR profiles were assessed by the disc diffusion method and trends over time were evaluated. Results A total 89,643 pediatric blood cultures were performed, and 10,621 pathogens were included in the analysis. Estimated minimum incidence rates of BSI for those ≤5 years of age fell from a peak of 11.4 per 1,000 persons in 2002 to 3.4 per 1,000 persons in 2017. Over two decades, resistance of Gram-negative pathogens to all empiric first-line antimicrobials (ampicillin/penicillin, gentamicin, ceftriaxone) among children ≤5 years increased from 3.4% to 30.2% (p<0.001). Among those ≤60 days, AMR to all first-line antimicrobials increased from 7.0% to 67.7% (p<0.001). Among children ≤5 years, Klebsiella spp. resistance to all first-line antimicrobial regimens increased from 5.9% to 93.7% (p<0.001). Conclusions The incidence of BSI among hospitalized children has decreased substantially over the last 20 years, although gains have been offset by increases in Gram-negative pathogens resistant to all empiric first-line antimicrobials. There is an urgent need to address the broader challenge of adapting IMCI guidelines to the local setting in the face of rapidly expanding AMR in childhood BSI

Dietary Patterns and Practices and Leucocyte Telomere Length: Findings from the UK Biobank

BACKGROUND: Shorter telomere length (TL) is associated with risk of several age-related diseases and decreased life span, but the extent to which dietary patterns and practices associate with TL is uncertain. OBJECTIVE: This study aimed to investigate the association of dietary patterns and practices and leucocyte TL (LTL). DESIGN: This was a cross-sectional study. PARTICIPANTS AND SETTING: Data collected voluntarily from up to 422,797 UK Biobank participants, during 2006-2010. MAIN OUTCOME MEASURES: LTL was measured as a ratio of the telomere repeat number to a single-copy gene and was loge-transformed and standardized (z-LTL). STATISTICAL ANALYSES PERFORMED: Adherence a priori to a Mediterranean-style diet was assessed through the MedDietScore. Principal component analysis was used to a posteriori extract the "Meat" and "Prudent" dietary patterns. Additional dietary practices considered were the self-reported adherence to "Vegetarian" diet, "Eating 5-a-day of fruit and vegetables" and "Abstaining from eggs/dairy/wheat/sugar." Associations between quintiles of dietary patterns or adherence to dietary practices with z-LTL were investigated through multivariable linear regression models (adjusted for demographic, lifestyle, and clinical characteristics). RESULTS: Adherence to the "Mediterranean" and the "Prudent" patterns, was positively associated with LTL, with an effect magnitude in z-LTL of 0.020 SD and 0.014 SD, respectively, for the highest vs the lowest quintile of adherence to the pattern (both P values < 0.05). Conversely, a reversed association between quintile of the "Meat" pattern and LTL was observed, with z-LTL being on average shorter by 0.025 SD (P = 6.12×10-05) for participants in the highest quintile of the pattern compared with the lowest quintile. For adherents to "5-a-day" z-LTL was on average longer by 0.027 SD (P = 5.36×10-09), and for "abstainers," LTL was shorter by 0.016 SD (P = 2.51×10-04). The association of LTL with a vegetarian diet was nonsignificant after adjustment for demographic, lifestyle, and clinical characteristics. CONCLUSIONS: Several dietary patterns and practices associated with beneficial health effects are significantly associated with longer LTL. However, the magnitude of the association was small, and any clinical relevance is uncertain