Associations between placental and cord blood malaria infection and fetal malnutrition in an area of malaria holoendemicity

The objective of this study was to determine the role of malaria in the etiology of fetal malnutrition in Nigeria. This study took place at the Neonatal and Maternity Units of the Wesley Guild Hospital, Ilesa, Nigeria. This is a prospective study of 304 consecutive, singleton, term live births delivered between January and August 2002. Anthropometric and clinical data were recorded. Fetal malnutrition (FM; failure to acquire adequate quantum of fat and muscle mass during intrauterine growth) was diagnosed using clinical assessment of fetal nutritional status (CANS) and the score (CANSCORE) adapted by Metcoff. The placenta tissues were examined for malaria pigments and parasites, and placental and cord blood smears were examined for parasites. Babies were followed up in the neonatal period for clinical malaria. Babies were grouped into those with malaria-infected placental and cord blood specimens and those without. The two groups were compared with regard to the proportions with FM and complications of FM. Three hundred four placental and cord blood specimens were examined for malaria. Of the 304, 101 (33.2%) of the placental and 67 (22.0%) of the cord blood specimens were positive for malaria. Sixty-six (21.7%) of the 304 babies had FM. Forty-four (66.7%) of the 66 placental blood specimens of babies with FM were positive for malaria, whereas 57 (24.0%) of the 238 placentae of babies without FM had placental malaria (chi(2) =42.5, P < 0.0001). Similarly, 27 (40.9%) of 66 babies with FM compared with 40 (16.8%) among 238 babies without FM had malaria parasites in the cord blood (chi(2) =17.5, P < 0.001). The means of birth weight, ponderal index, and placenta weight were significantly lower among the babies of mothers with malaria-infected placentae than those without (P < 0.05 in all cases). Lack of antenatal care, primiparity, and failure to have chemoprophylaxis against malaria were the maternal factors found to be associated with placental malaria infection. Placental malaria is a major factor in the etiology of FM in Nigeria.     

Prevention of mother to child transmission of HIV infection in Pacific countries

Introduction: A generalized epidemic of HIV infection has been evolving in Papua New Guinea over the last decade, whereas in other Pacific Island countries and territories (PICT) HIV transmission has generally been less widespread. Programmes to detect HIV infection in pregnant women and to prevent mother to child transmission (MTCT) during either delivery or breast‐feeding can decrease the incidence of infection in infants. The limited health infrastructure present in some PICT may delay the implementation of effective programmes to decrease MTCT of HIV. Methods: We used a standardized questionnaire to survey health‐care providers in 22 PICT for information on the epidemiology of HIV infection and strategies used during 2004 to prevent MTCT of HIV infection in their country. We supplemented these survey responses with data obtained from regional organizations supporting national responses to HIV. Results: We obtained responses from 21 PICT. The reported prevalence of known HIV infection was >150 per 100 000 persons in Papua New Guinea, approximately 100 per 100 000 persons in French Polynesia, Guam, New Caledonia and Tuvalu and <50 per 100 000 persons in the remaining 14 PICT. Other than in Papua New Guinea, where an estimated 500 pregnant women had HIV infection diagnosed in 2004, reported HIV infection among pregnant women was rare. Ten PICT reported that an HIV antibody test was offered as a routine component of antenatal care and 11 reported that antiretroviral medications were available for the prevention of MTCT of HIV infection. Conclusion: The prevalence of HIV infection differs greatly between PICT with a varying risk of MTCT of HIV infection. Successful prevention of MTCT of HIV infection throughout the PICT will require improved uptake of antenatal HIV antibody testing and better access to antiretroviral medications.     

Basophil effector function and homeostasis during helminth infection

Basophils are effector cells of the innate immune system that are associated with allergic inflammation and infections with helminth parasites. However, their development and in vivo functions are largely unknown. Here, we characterize basophil development, turnover, tissue localization, and effector function during infection with the helminth Nippostrongylus brasiliensis. Our results demonstrate that under homeostatic conditions basophils have a lifespan of about 60 hours. N brasiliensis-induced basophilia is caused by increased de novo production of basophils in the bone marrow. Basophils were found near the marginal zone in the red pulp of the spleen, in the lamina propria of the small intestine, and in the lung parenchyma. Activated basophils promoted systemic eosinophilia, were associated with differentiation of alternatively activated macrophages in the lung, and contributed to efficient worm expulsion, demonstrating that basophils play a crucial role as effector cells in type 2 immune responses.     

Iron homeostasis in beta-thalassemic mice

To explore the pathogenesis of nontransfusional iron overload in iron- loading anemia, we examined features of external iron exchange, internal iron kinetics, and tissue iron burden in adult mice with inherited gene-deletion beta-thalassemia. Mice homozygous for beta- thalassemia display moderate anemia, reticulocytosis, and shortened red cell survival, whereas heterozygous carriers appear hematologically normal. Quantitative iron determination revealed that iron content and concentration in liver, spleen, and kidney, but not heart, were far higher (P less than .01) in 15-to 35-week old homozygous thalassemic mice than in age-matched normal and heterozygous controls; of these tissues, iron content increased with age only in kidneys (P = .01) of homozygous affected mice. Although plasma iron levels were only minimally elevated in homozygotes, plasma iron turnover was threefold greater (P less than .001) than that seen in heterozygote controls. Nevertheless hyperabsorption of enteric radioiron, discernible among homozygous thalassemic mice as late as 6 to 8 weeks after birth, was not observed in older mice, additionally, thalassemic and control mice at 18 to 34 weeks showed comparable iron excretion after intravenous radioiron. We conclude that adult mice with beta-thalassemia regain balanced external iron exchange, despite substantial tissue iron excess and accelerated internal iron transit.     

Effect of placental malaria and HIV infection on the antibody responses to Plasmodium falciparum in infants

BACKGROUND: Placental malaria (PM) and maternal infection with human immunodeficiency virus (HIV) type 1 have been shown to affect infant morbidity and immune responses to Plasmodium falciparum. We studied the effects of PM and HIV infection on the antimalarial antibody responses and morbidity outcomes of infants throughout the first year of life. METHODS: A total of 411 Kenyan infants who were born to mothers who were singly or dually infected with PM and/or HIV had their levels of immunoglobulin G antibody to 6 P. falciparum antigens/epitopes (apical membrane antigen-1, erythrocyte-binding antigen-175; liver-stage antigen-1 [LSA-1], circumsporozoite protein [CSP], merozoite surface protein-2, and rhoptry-associated protein-1 [RAP-1]) and to tetanus toxoid (TT) tested using enzyme-linked immunosorbent assay. RESULTS: PM had little effect on the antibody responses of infants, whereas maternal HIV infection resulted in decreased levels of antibody to LSA-1, CSP, and RAP-1 epitopes at birth, compared with the absence of PM and maternal HIV infection (P = .0063). Levels of antibodies to TT were significantly reduced in infants born to mothers coinfected with HIV and PM, compared with the levels noted in infants born to HIV-negative mothers (P = .0003). In HIV-infected infants, levels of antibody to TT were reduced, but levels of antibody to malarial antigens were not. Antimalarial antibody levels were positively associated with malaria-related morbidity outcomes. CONCLUSION: Infant HIV infection and maternal coinfection with HIV and PM negatively influence antibody responses to TT, but not those to malarial antigens, in infants. Antimalarial antibodies rarely showed protective associations with morbidity in infants and were more often a marker for malaria exposure and risk of infection.     

Iron homeostasis in pregnancy and spontaneous abortion

During pregnancy, iron requirements are increased to support maternal erythropoietic expansion and fetal growth and development. To meet these requirements, dietary iron absorption increases, and available iron stores are mobilized. These adjustments are thought to be in large part mediated by the iron-regulatory hormone hepcidin, which controls the concentrations of ferroportin, the sole exporter of iron into the extracellular fluid and blood plasma. Hepcidin regulation of iron availability during healthy and abnormal pregnancies is not well understood. In our cross-sectional study, we compared hepcidin, iron and hematological parameters between nonpregnant control women, healthy pregnant women in the first and second trimester, and women with spontaneous abortion in the first trimester. We found that in healthy pregnancy, hepcidin increased in the first trimester compared with nonpregnant women, but then decreased during the second trimester. The second trimester hepcidin levels decreased despite stable serum iron concentrations, suggesting active suppression of hepcidin, presumably to enhance iron availability as iron demand increases. In women with spontaneous abortion during the first trimester, hepcidin, serum iron, and ferritin concentrations were all increased compared with the first trimester healthy pregnancy. Although the specific mechanisms remain to be determined, our findings demonstrate that maternal hepcidin is regulated by signals related to the progression of pregnancy, and that pregnancy loss is associated with profound changes in maternal iron metabolism. These observations highlight the existence of fetoplacental signals that modulate maternal iron homeostasis.     

Maternal HIV infection and placental malaria reduce transplacental antibody transfer and tetanus antibody levels in newborns in Kenya

BACKGROUND: In clinical trials, maternal tetanus toxoid (TT) vaccination is effective in protecting newborns against tetanus infection, but inadequate placental transfer of tetanus antibodies may contribute to lower-than-expected rates of protection in routine practice. We studied the effect of placental malaria and maternal human immunodeficiency virus (HIV) infection on placental transfer of antibodies to tetanus. METHODS: A total of 704 maternal-cord paired serum samples were tested by ELISA for antibodies to tetanus. The HIV status of all women was determined by an immunoglobulin G antibody-capture particle-adherence test, and placental malaria was determined by placental biopsy. Maternal history of TT vaccination was recorded. RESULTS: Tetanus antibody levels were reduced by 52% (95% confidence interval [CI], 30%-67%) in newborns of HIV-infected women and by 48% (95% CI, 26%-62%) in newborns whose mothers had active-chronic or past placental malaria. Thirty-seven mothers (5.3%) and 55 newborns (7.8%) had tetanus antibody levels <0.1 IU/mL (i.e., were seronegative). Mothers' self-reported history of lack of tetanus immunization was the strongest predictor of seronegativity and of tetanus antibody levels in maternal and cord serum. CONCLUSION: Malarial and HIV infections may hinder efforts to eliminate maternal and neonatal tetanus, making implementation of the current policy for mass vaccination of women of childbearing age an urgent priority.     

Integration of mother and child health services in Ethiopia

In Wollo region of Ethiopia, various non-governmental officers have been working closely with each other and with the Regional Health Department to implement the policy of daily integrated mother and child health services. The record cards, registers, procedures and training courses of the separate 'vertically' organized services were brought together to enable the development of a model integrated service. There were improvements in accessibility, acceptability and output of the services. The system was evaluated by a joint Ministry of Health and UNICEF team, and was adopted for use in the rest of Ethiopia.     

A study on malaria infection during the acute stage of measles infection

The recognized high mortality from measles in Africa is considered to be partly due to the flare-up of concomitant malaria infection. In 1987 there was a measles epidemic in the Rufiji Delta, Tanzania, in spite of recent vaccination campaigns. A comparative study was therefore conducted on the densities of malaria parasites in children during the acute stage of measles (67 consecutive cases, aged 5 months-19 years). The period of study was March-June, the peak season for malaria transmission. For each measles patient, a blood film was concomitantly taken from an asymptomatic age-matched child from the same village. Of 67 children with measles, 17 (25%) had parasitaemia ranging from 8 to 2480 parasites microliter-1 blood. Out of 67 asymptomatic control children 59 (88%) had parasitaemia ranging from 8 to 3400 parasites microliter-1 blood. This study indicates that malaria densities were lower during the acute stage of measles than in healthy children. The contribution of malaria to mortality in children with acute measles may be questioned.     

6-Thioguanine for Crohn's disease during pregnancy: Thiopurine metabolite measurements in both mother and child

6-Thioguanine is used as an escape thiopurine for treating inflammatory bowel disease patients intolerant or refractory to azathioprine, 6-mercaptopurine or methotrexate. Case reports show conflicting data on the use of 6-thioguanine throughout pregnancy. The administration of the standard thiopurines is believed to be relatively safe. We describe two patients with Crohn's disease treated with low-dose 6-thioguanine during all trimesters of their pregnancies. The pregnancies resulted in two healthy infants: without congenital abnormalities, laboratory signs of myelosuppression or hepatocellular injury. Thiopurine metabolites were measured in mother and infant. Significantly lower levels of 6-thioguaninenucleotides were found in the erythrocytes of the infant compared to the mother (ratio 1:12). Further studies are needed to determine the clinical importance of thiopurine metabolite measurements during pregnancy in mother and child.     

6-Thioguanine for Crohn's disease during pregnancy: thiopurine metabolite measurements in both mother and child

6-Thioguanine is used as an escape thiopurine for treating inflammatory bowel disease patients intolerant or refractory to azathioprine, 6-mercaptopurine or methotrexate. Case reports show conflicting data on the use of 6-thioguanine throughout pregnancy. The administration of the standard thiopurines is believed to be relatively safe. We describe two patients with Crohn's disease treated with low-dose 6-thioguanine during all trimesters of their pregnancies. The pregnancies resulted in two healthy infants: without congenital abnormalities, laboratory signs of myelosuppression or hepatocellular injury. Thiopurine metabolites were measured in mother and infant. Significantly lower levels of 6-thioguaninenucleotides were found in the erythrocytes of the infant compared to the mother (ratio 1:12). Further studies are needed to determine the clinical importance of thiopurine metabolite measurements during pregnancy in mother and child.     

Prediction of Plasmodium falciparum placental infection according to the time of infection during pregnancy

Malarial infection during pregnancy leads to placental infection, a known risk factor for low birth weight. Whether the stage of pregnancy at infection has a differential influence on these effects is not clearly known, but may be of importance for prevention strategies, including intermittent preventive treatment of pregnant women. Malaria infection during early (before 20 weeks), middle (20-28 weeks), or late (after 28 weeks) pregnancy was evaluated by logistic regression and receiver operating characteristics analysis in relation to placental infection in pregnant Senegalese women. Plasmodium falciparum infections during late pregnancy are strongly related to placental infection, as well as those that occur in middle pregnancy. Knowledge of parasitological events over the entire duration of pregnancy permits a highly accurate prediction of placental infection. Not only malaria infections during late pregnancy increase the likelihood of placental infection. The current policy of intermittent preventive treatment of pregnant women, which implies an initial antimalarial cure after 20 weeks of pregnancy, will not avoid early infections. An earlier initiation of malaria prevention might improve its efficacy.