Observed and expected frequencies of structural hemoglobin variants in newborn screening surveys in Africa and the Middle East: deviations from Hardy-Weinberg equilibrium.

Purpose: Our objective was to compare observed and expected genotype proportions from newborn screening surveys of structural hemoglobin variants.

Methods: We conducted a systematic review of newborn screening surveys of hemoglobins S and C in Africa and the Middle East. We compared observed frequencies to those expected assuming Hardy-Weinberg equilibrium (HWE).

Incidence and predictors of attrition from antiretroviral care among adults in a rural HIV clinic in Coastal Kenya: a retrospective cohort study.

Background: Scale up of antiretroviral therapy (ART) has led to substantial declines in HIV related morbidity and mortality. However, attrition from ART care remains a major public health concern and has been identified as one of the key reportable indicators in assessing the success of ART programs. This study describes the incidence and predictors of attrition among adults initiating ART in a rural HIV clinic in Coastal Kenya.

Combinatorial effects of malaria season, iron deficiency, and inflammation determine plasma hepcidin concentration in African children.

Hepcidin is the master regulatory hormone that governs iron homeostasis and has a role in innate immunity. Although hepcidin has been studied extensively in model systems, there is less information on hepcidin regulation in global health contexts where iron deficiency (ID), anemia, and high infectious burdens (including malaria) all coexist but fluctuate over time. We evaluated iron status, hepcidin levels, and determinants of hepcidin in 2 populations of rural children aged ≤8 years, in the Gambia and Kenya (total n = 848), at the start and end of a malaria season.

HE BURDEN AND CHALLENGES OF NEONATAL TETANUS IN KILIFI DISTRICT, KENYA--2004-7.

Objectives: To describe the incidence of neonatal tetanus (NNT) and to describe the trends between 2004 and 2007; to show the geographical distribution of NNT in Kilifi district and to describe routine immunisation coverage, catch-up campaigns and mop-ups.

Design: Retrospective study

Setting: Kilifi district, Coastal Kenya

Subjects: Children diagnosed with Neonatal Tetanus (NNT) attending Health facilities in the District.

Results: The incidence of NNT in Kilifi increased from 0.

Influenza surveillance among children with pneumonia admitted to a district hospital in coastal Kenya, 2007-2010.

Background: Influenza data gaps in sub-Saharan Africa include incidence, case fatality, seasonal patterns, and associations with prevalent disorders.

Methods: Nasopharyngeal samples from children aged <12 years who were admitted to Kilifi District Hospital during 2007-2010 with severe or very severe pneumonia and resided in the local demographic surveillance system were screened for influenza A, B, and C viruses by molecular methods. Outpatient children provided comparative data.

World distribution, population genetics, and health burden of the hemoglobinopathies.

Although information about the precise world distribution and frequency of the inherited hemoglobin disorders is still limited, there is no doubt that they are going to pose an increasing burden on global health resources in the future. Their high frequency is a reflection of natural selection combined with a high frequency of consanguineous marriages in many countries, together with an epidemiological transition; whereby, as public health measures improve in the poorer countries of the world, more babies with these disorders are surviving to present for treatment.

Risk and causes of paediatric hospital-acquired bacteraemia in Kilifi District Hospital, Kenya: a prospective cohort study.

Background: In sub-Saharan Africa, community-acquired bacteraemia is an important cause of illness and death in children. Our aim was to establish the magnitude and causes of hospital-acquired (nosocomial) bacteraemia in African children.

Methods: We reviewed prospectively collected surveillance data of 33,188 admissions to Kilifi District Hospital, Kenya, between April 16, 2002, and Sept 30, 2009.

Acquisition of naturally occurring antibody responses to recombinant protein domains of Plasmodium falciparum erythrocyte membrane protein 1.

Background: Antibodies targeting variant antigens expressed on the surface of Plasmodium falciparum infected erythrocytes have been associated with protection from clinical malaria. The precise target for these antibodies is unknown. The best characterized and most likely target is the erythrocyte surface-expressed variant protein family Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1).

Failure to respond to the surface of Plasmodium falciparum infected erythrocytes predicts susceptibility to clinical malaria amongst African children.

Following infection with Plasmodium falciparum malaria, children in endemic areas develop antibodies specific to antigens on the parasite-infected red cell surface of the infecting isolate, antibodies associated with protection against subsequent infection with that isolate. In some circumstances induction of antibodies to heterologous parasite isolates also occurs and this has been suggested as evidence for cross-reactivity of responses against the erythrocyte surface. The role of these relatively cross-reactive antibodies in protection from clinical malaria is currently unknown.

The haptoglobin 2-2 genotype is associated with a reduced incidence of Plasmodium falciparum malaria in children on the coast of Kenya.

Background: Haptoglobin (Hp) genotype determines the efficiency of hemoglobin clearance after malaria-induced hemolysis and alters antioxidant and immune functions. The Hp2 allele is thought to have spread under strong selection pressure, but it is unclear whether this is due to protection from malaria or other diseases.

Methods: We monitored the incidence of febrile malaria and other childhood illnesses with regard to Hp genotype in a prospective cohort of 312 Kenyan children during 558.

Co-inheritance of alpha+-thalassaemia and sickle trait results in specific effects on haematological parameters.

Both the sickle cell trait (HbAS) and alpha(+)-thalassaemia are common in many tropical areas. While their individual haematological effects are well described, few studies describe their effects when inherited together. We present data from the Kenyan coast, which suggest that HbAS and alpha(+)-thalassaemia may interact to produce specific effects on haematological parameters.

The effect of alpha+-thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya.

Background: The alpha-thalassaemias are the commonest genetic disorders of humans. It is generally believed that this high frequency reflects selection through a survival advantage against death from malaria; nevertheless, the epidemiological description of the relationships between alpha-thalassaemia, malaria, and other common causes of child mortality remains incomplete.

Methods And Findings: We studied the alpha+-thalassaemia-specific incidence of malaria and other common childhood diseases in two cohorts of children living on the coast of Kenya.

Appendicitis at Kenyatta National Hospital, Nairobi.

Background: Appendicitis still remains a diagnostic challenge particularly in women and extremes of age. The incidence of appendicectomy for suspected appendicitis is higher but declining in the developed countries in contrast with a low but increasing incidence in Africa.

Objective: To describe the characteristics of appendicitis at Kenyatta National Hospital, with emphasis on epidemiological oddities.

Negative epistasis between the malaria-protective effects of alpha+-thalassemia and the sickle cell trait.

The hemoglobinopathies, disorders of hemoglobin structure and production, protect against death from malaria. In sub-Saharan Africa, two such conditions occur at particularly high frequencies: presence of the structural variant hemoglobin S and alpha(+)-thalassemia, a condition characterized by reduced production of the normal alpha-globin component of hemoglobin. Individually, each is protective against severe Plasmodium falciparum malaria, but little is known about their malaria-protective effects when inherited in combination.

Sickle cell trait and the risk of Plasmodium falciparum malaria and other childhood diseases.

Background: The gene for sickle hemoglobin (HbS) is a prime example of natural selection. It is generally believed that its current prevalence in many tropical populations reflects selection for the carrier form (sickle cell trait [HbAS]) through a survival advantage against death from malaria. Nevertheless, >50 years after this hypothesis was first proposed, the epidemiological description of the relationships between HbAS, malaria, and other common causes of child mortality remains incomplete.

An immune basis for malaria protection by the sickle cell trait.

Background: Malaria resistance by the sickle cell trait (genotype HbAS) has served as the prime example of genetic selection for over half a century. Nevertheless, the mechanism of this resistance remains the subject of considerable debate. While it probably involves innate factors such as the reduced ability of Plasmodium falciparum parasites to grow and multiply in HbAS erythrocytes, recent observations suggest that it might also involve the accelerated acquisition of malaria-specific immunity.

Cytokine mRNA expression and iron status in children living in a malaria endemic area.

Iron deficiency has been reported to affect both malaria pathogenesis and cell-mediated immune responses; however, it is unclear whether the protection afforded by iron deficiency is mediated through direct effects on the parasite, through immune effector functions or through both. We have determined cytokine mRNA expression levels in 59 children living in a malaria endemic area on the coast of Kenya who we selected on the basis of their biochemical iron status. Real-time quantitative reverse transcriptase polymerase chain reaction analysis of cytokine mRNA levels of peripheral blood mononuclear cells (PBMC) obtained from these children showed an association between interleukin-4 (IL-4) mRNA levels and all the biochemical indices of iron that we measured.

Malaria and nutritional status in children living on the coast of Kenya.

Background: The relation between malnutrition and malaria is controversial. On the one hand, malaria may cause malnutrition, whereas on the other hand, malnutrition itself may modulate susceptibility to the disease.

Objective: The objective was to investigate the association between Plasmodium falciparum malaria and malnutrition in a cohort of Kenyan children.

Iron deficiency and malaria among children living on the coast of Kenya.

Both iron deficiency and malaria are common in much of sub-Saharan Africa, and the interaction between these conditions is complex. To investigate the association between nutritional iron status, immunoglobulins, and clinical Plasmodium falciparum malaria, we determined the incidence of malaria in a cohort of children between the ages of 8 months and 8 years who were living on the Kenyan coast. Biochemical iron status and malaria-specific immune responses were determined during 2 cross-sectional surveys.

Abnormal blood glucose concentrations on admission to a rural Kenyan district hospital: prevalence and outcome.

Aims: To determine the prevalence, clinical characteristics, and outcome of hypoglycaemia on admission in children at a rural Kenyan district hospital.

Methods: Observational study of 3742 children (including 280 neonates) in Kilifi District Hospital, Kenya.

Main Outcome Measures: hypoglycaemia (blood glucose <2.