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Clinical and Epidemiological Implications of 24-Hour Ambulatory Blood Pressure Monitoring for the Diagnosis of Hypertension in Kenyan Adults: A Population-Based Study

BACKGROUND: The clinical and epidemiological implications of using ambulatory blood pressure monitoring (ABPM) for the diagnosis of hypertension have not been studied at a population level in sub-Saharan Africa. We examined the impact of ABPM use among Kenyan adults. METHODS AND RESULTS: We performed a nested case-control study of diagnostic accuracy. We selected an age-stratified random sample of 1248 adults from the list of residents of the Kilifi Health and Demographic Surveillance System in Kenya. All participants underwent a screening blood pressure (BP) measurement. All those with screening BP >/=140/90 mm Hg and a random subset of those with screening BP <140/90 mm Hg were invited to undergo ABPM. Based on the 2 tests, participants were categorized as sustained hypertensive, masked hypertensive, "white coat" hypertensive, or normotensive. Analyses were weighted by the probability of undergoing ABPM. Screening BP >/=140/90 mm Hg was present in 359 of 986 participants, translating to a crude population prevalence of 23.1% (95% CI 16.5-31.5%). Age standardized prevalence of screening BP >/=140/90 mm Hg was 26.5% (95% CI 19.3-35.6%). On ABPM, 186 of 415 participants were confirmed to be hypertensive, with crude prevalence of 15.6% (95% CI 9.4-23.1%) and age-standardized prevalence of 17.1% (95% CI 11.0-24.4%). Age-standardized prevalence of masked and white coat hypertension were 7.6% (95% CI 2.8-13.7%) and 3.8% (95% CI 1.7-6.1%), respectively. The sensitivity and specificity of screening BP measurements were 80% (95% CI 73-86%) and 84% (95% CI 79-88%), respectively. BP indices and validity measures showed strong age-related trends. CONCLUSIONS: Screening BP measurement significantly overestimated hypertension prevalence while failing to identify approximately 50% of true hypertension diagnosed by ABPM. Our findings suggest significant clinical and epidemiological benefits of ABPM use for diagnosing hypertension in Kenyan adults.
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The Malaria-High Blood Pressure Hypothesis

RATIONALE: Several studies have demonstrated links between infectious diseases and cardiovascular conditions. Malaria and hypertension are widespread in many low- and middle-income countries, but the possible link between them has not been considered. OBJECTIVE: In this article, we outline the basis for a possible link between malaria and hypertension and discuss how the hypothesis could be confirmed or refuted. METHODS AND RESULTS: We reviewed published literature on factors associated with hypertension and checked whether any of these were also associated with malaria. We then considered various study designs that could be used to test the hypothesis. Malaria causes low birth weight, malnutrition, and inflammation, all of which are associated with hypertension in high-income countries. The hypothetical link between malaria and hypertension can be tested through the use of ecological, cohort, or Mendelian randomization studies, each of which poses specific challenges. CONCLUSIONS: Confirmation of the existence of a causative link with malaria would be a paradigm shift in efforts to prevent and control hypertension and would stimulate wider research on the links between infectious and noncommunicable disease.
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“When you give birth you will not be without your mother” A mixed methods study of advice on breastfeeding for first-time mothers in rural coastal Kenya

BACKGROUND: Exclusive breastfeeding for the first 6 months of life is currently recommended by the World Health Organization, but mixed feeding earlier than this commonly occurs in rural coastal Kenya. Mothers may receive conflicting advice on breastfeeding from various sources including health workers, relatives and community members. We aimed to find out how first-time mothers learn to breastfeed, who advises them on infant feeding and what advice they obtain in case of any breastfeeding problems. METHODS: To identify advisers, a questionnaire on socio-demographic status, place of delivery, household members, education and help received on breastfeeding, breastfeeding problems, name of advisers and their relationship to the mothers was administered to 50 new first-time mothers in Jaribuni, Kilifi (population approximately 18,000). Summary statistics were obtained using frequencies, medians and interquartile ranges (IQR). Focus group discussions (FGDs) were held amongst 4 groups of mothers who had answered questionnaires; 4 groups of their named advisers; and 1 group of community health workers in order to explore breastfeeding practices, problems and advice given. FGDs were analysed by thematic framework analysis. RESULTS: First-time mothers were young (median age 18, IQR 17-21, range 14-26 years) and 42 % were single. Living in extended families was the norm and married women lived with their husband's family. All had a female family member or neighbour helping with childcare in the perinatal period. The main advisers on breastfeeding were their mother or older female members of their husband's family. Married first-time mothers felt obliged to follow their mother-in-law's advice to maintain good relationships and show respect within the household. Breastfeeding problems were reported by 80 % of respondents. Nipple pain (56 %) was the most reported problem, then breast engorgement (48 %) and insufficient milk supply (38 %). Most problems were treated at home without consultation with health workers. Concerns were raised about co-sleeping, breastfeeding whilst lying down, and insufficient milk supply. Advisers would like more information on breastfeeding in order to help mothers. CONCLUSIONS: Interventions to increase knowledge of, and facilitate optimal breastfeeding practices in first-time mothers should include those family members who advise and assist with childcare around the time of delivery.
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Building Learning Health Systems to Accelerate Research and Improve Outcomes of Clinical Care in Low- and Middle-Income Countries

Mike English and colleagues argue that as efforts are made towards achieving universal health coverage it is also important to build capacity to develop regionally relevant evidence to improve healthcare.
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Serological Conservation of Parasite-Infected Erythrocytes Predicts Plasmodium falciparum Erythrocyte Membrane Protein 1 Gene Expression but Not Severity of Childhood Malaria

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), expressed on P. falciparum-infected erythrocytes, is a major family of clonally variant targets of naturally acquired immunity to malaria. Previous studies have demonstrated that in areas where malaria is endemic, antibodies to infected erythrocytes from children with severe malaria tend to be more seroprevalent than antibodies to infected erythrocytes from children with nonsevere malaria. These data have led to a working hypothesis that PfEMP1 variants associated with parasite virulence are relatively conserved in structure. However, the longevity of such serologically conserved variants in the parasite population is unknown. Here, using infected erythrocytes from recently sampled clinical P. falciparum samples, we measured serological conservation using pools of antibodies in sera that had been sampled 10 to 12 years earlier. The serological conservation of infected erythrocytes strongly correlated with the expression of specific PfEMP1 subsets previously found to be associated with severe malaria. However, we found no association between serological conservation per se and disease severity within these data. This contrasts with the simple hypothesis that P. falciparum isolates with a serologically conserved group of PfEMP1 variants cause severe malaria. The data are instead consistent with periodic turnover of the immunodominant epitopes of PfEMP1 associated with severe malaria.
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Serological Conservation of Parasite-Infected Erythrocytes Predicts Plasmodium falciparum Erythrocyte Membrane Protein 1 Gene Expression but Not Severity of Childhood Malaria

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), expressed on P. falciparum-infected erythrocytes, is a major family of clonally variant targets of naturally acquired immunity to malaria. Previous studies have demonstrated that in areas where malaria is endemic, antibodies to infected erythrocytes from children with severe malaria tend to be more seroprevalent than antibodies to infected erythrocytes from children with nonsevere malaria. These data have led to a working hypothesis that PfEMP1 variants associated with parasite virulence are relatively conserved in structure. However, the longevity of such serologically conserved variants in the parasite population is unknown. Here, using infected erythrocytes from recently sampled clinical P. falciparum samples, we measured serological conservation using pools of antibodies in sera that had been sampled 10 to 12 years earlier. The serological conservation of infected erythrocytes strongly correlated with the expression of specific PfEMP1 subsets previously found to be associated with severe malaria. However, we found no association between serological conservation per se and disease severity within these data. This contrasts with the simple hypothesis that P. falciparum isolates with a serologically conserved group of PfEMP1 variants cause severe malaria. The data are instead consistent with periodic turnover of the immunodominant epitopes of PfEMP1 associated with severe malaria.
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Global selection of Plasmodium falciparum virulence antigen expression by host antibodies

Parasite proteins called PfEMP1 that are inserted on the surface of infected erythrocytes, play a key role in the severe pathology associated with infection by the Plasmodium falciparum malaria parasite. These proteins mediate binding of infected cells to the endothelial lining of blood vessels as a strategy to avoid clearance by the spleen and are major targets of naturally acquired immunity. PfEMP1 is encoded by a large multi-gene family called var. Mutually-exclusive transcriptional switching between var genes allows parasites to escape host antibodies. This study examined in detail the patterns of expression of var in a well-characterized sample of parasites from Kenyan Children. Instead of observing clear inverse relationships between the expression of broad sub-classes of PfEMP1, we found that expression of different PfEMP1 groups vary relatively independently. Parasite adaptation to host antibodies also appears to involve a general reduction in detectable var gene expression. We suggest that parasites switch both between different PfEMP1 variants and between high and low expression states. Such a strategy could provide a means of avoiding immunological detection and promoting survival under high levels of host immunity.
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Global selection of Plasmodium falciparum virulence antigen expression by host antibodies

Parasite proteins called PfEMP1 that are inserted on the surface of infected erythrocytes, play a key role in the severe pathology associated with infection by the Plasmodium falciparum malaria parasite. These proteins mediate binding of infected cells to the endothelial lining of blood vessels as a strategy to avoid clearance by the spleen and are major targets of naturally acquired immunity. PfEMP1 is encoded by a large multi-gene family called var. Mutually-exclusive transcriptional switching between var genes allows parasites to escape host antibodies. This study examined in detail the patterns of expression of var in a well-characterized sample of parasites from Kenyan Children. Instead of observing clear inverse relationships between the expression of broad sub-classes of PfEMP1, we found that expression of different PfEMP1 groups vary relatively independently. Parasite adaptation to host antibodies also appears to involve a general reduction in detectable var gene expression. We suggest that parasites switch both between different PfEMP1 variants and between high and low expression states. Such a strategy could provide a means of avoiding immunological detection and promoting survival under high levels of host immunity.
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The role of PfEMP1 as targets of naturally acquired immunity to childhood malaria: prospects for a vaccine

The Plasmodium falciparum erythrocyte membrane protein 1 antigens that are inserted onto the surface of P. falciparum infected erythrocytes play a key role both in the pathology of severe malaria and as targets of naturally acquired immunity. They might be considered unlikely vaccine targets because they are extremely diverse. However, several lines of evidence suggest that underneath this molecular diversity there are a restricted set of epitopes which may act as effective targets for a vaccine against severe malaria. Here we review some of the recent developments in this area of research, focusing on work that has assessed the potential of these molecules as possible vaccine targets.
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The role of PfEMP1 as targets of naturally acquired immunity to childhood malaria: prospects for a vaccine

The Plasmodium falciparum erythrocyte membrane protein 1 antigens that are inserted onto the surface of P. falciparum infected erythrocytes play a key role both in the pathology of severe malaria and as targets of naturally acquired immunity. They might be considered unlikely vaccine targets because they are extremely diverse. However, several lines of evidence suggest that underneath this molecular diversity there are a restricted set of epitopes which may act as effective targets for a vaccine against severe malaria. Here we review some of the recent developments in this area of research, focusing on work that has assessed the potential of these molecules as possible vaccine targets.
Read More