PubMed Health⌕ Search

Biomedical subjects

D L Heymann

Publications and source records attributed to D L Heymann.

At least 37 records · Page 2Linked to original sources
PubMed1996

Comparability of treatment groups and risk factors for parasitemia at the first antenatal clinic visit in a study of malaria treatment and prevention in pregnancy in rural Malawi.

The problems of Plasmodium falciparum infection in pregnant women have been described in numerous sub-Saharan African countries, but the frequency of parasitemia at the first antenatal visit and risk factors for infection have not been fully investigated. During a prospective antimalarial treatment and prophylaxis trial in pregnant women in Malawi (three groups receiving a chloroquine regimen and one group receiving a mefloquine regimen), we examined women at their first antenatal clinic visit to evaluate these issues and to verify that subjects in the study treatment/prevention arms were similar. Among 4,127 women with enrollment blood smear results, 1,836 (44.5%) were parasitemic. The highest infection rates and densities were observed in primigravidas (66% infected, geometric mean parasite density [GMPD] = 1,588 parasites/mm3 of whole blood), followed by second pregnancies (46% infected, GMPD = 615 parasites/mm3) and subsequent pregnancies (29% infected, GMPD = 238 parasites/mm3), (P < 10(-6) for both infection prevalence and density, by chi-square test for trend). Significant risk factors for parasitemia at first antenatal clinic visit in a multivariate model included low gravidity, high transmission season, no use of prophylaxis before first antenatal clinic visit, young age (< 20 years), human immunodeficiency virus (HIV) infection, low hematocrit, short stature, and second trimester (compared with third trimester). Women in the different treatment arms of the study were generally similar in many characteristics; statistically significant differences, where present, were small. Targeting malaria control efforts to women in their first or second pregnancy and during the high transmission season will be an important strategy to reach most parasitemic women and minimize resource expenditure. Women infected with HIV had a 55% increased risk of parasitemia at their first antenatal clinic visit and may represent an additional important risk group whose numbers may be increasing and who may benefit from identification and management for malaria.

Adolescent↗
PubMed1996

The problem of malaria and malaria control in pregnancy in sub-Saharan Africa.

Plasmodium falciparum infection in pregnant women frequently leads to placental infection and low birth weight (< 2,500 grams) of the infant, particularly in the areas of high malaria transmission found in sub-Saharan Africa. Low birth weight is widely known to be an important risk factor for early infant mortality. To reduce the risk that maternal infection poses to child survival, many antenatal clinic programs recommend and provide antimalarial chemoprophylaxis, often with chloroquine (CQ) as a recommended element for antenatal care. Prior to the 1980s, despite widespread advocacy for this intervention, little was known about the effect of this intervention strategy. As an introduction to the Mangochi Malaria Research Project, which examined the efficacy of several antimalarial regimens using CQ or mefloquine in pregnant women in Malawi, we describe the background of knowledge regarding malaria infection in pregnant African women and the important elements of an intervention and prevention strategy.

Africa South of the Sahara↗
PubMed1996

Malaria parasite infection during pregnancy and at delivery in mother, placenta, and newborn: efficacy of chloroquine and mefloquine in rural Malawi.

Despite international recommendations to use malaria treatment and prevention in pregnant women in malaria-endemic areas, few studies have evaluated the efficacy of available antimalarial regimens. This issue is of particular concern in the face of spreading chloroquine (CQ)-resistance of Plasmodium falciparum in malarious areas of sub-Saharan Africa. In a prospective trial in rural Malawian pregnant women, we examined three regimens using CQ (including the existing national policy regimen) and one regimen using mefloquine (MQ). The efficacy of the regimens was determined by comparing rates of clearance of initial parasitemia; prevention of breakthrough infection; and parasitemia at delivery in maternal peripheral blood, placental blood, and in infant umbilical cord blood. Among 1,528 parasitemic women at enrollment, 281 (18.4%) had persistent infections; and among 1,852 initially aparasitemic women, 320 (17.3%) had breakthrough parasitemia on one or more follow-up visits. Compared with women on MQ, women on a CQ regimen were at significantly greater risk of persistent and breakthrough infection (odds ratios [OR] = 30.9 and 11.1, respectively, P < 10(-6)). Other significant risk factors for persistent and breakthrough infections in a multivariate model included first pregnancy; enrollment in the rainy or postrainy season; maternal age < or = 25 years; seropositivity to the human immunodeficiency virus (HIV) (persistent infections only); and no use of antimalarial prophylaxis before enrollment (breakthrough infections only). At delivery, compared with women on MQ, women on a CQ regimen were at significantly greater risk of peripheral, placental, or umbilical cord blood parasitemia (OR = 8.7, 7.4, and 4.1, respectively, P < 10(-6)). Additional risk factors for parasitemia at delivery in multivariate models included first pregnancy; delivery in the rainy or postrainy season; HIV-seropositivity; and maternal age < or = 25 years (risk for peripheral and placental blood parasitemia only). Maternal anemia (hematocrit < 30%) at enrollment or at delivery was not associated with persistent or breakthrough parasitemia or parasitemia at deliver in these multivariate models. While factors leading to increased malaria parasite exposure (high transmission seasons) and lowered or altered host immune response (low pregnancy number, young age, and HIV infection) are important risk factors for malaria in pregnant women, the use of an ineffective intervention (CQ in a setting with CQ-resistant parasites) was the most important determinant of P. falciparum parasitemia in these pregnant women. Strategies to reduce the impact of malaria in pregnant women must use efficacious interventions and may need to consider targeting the intervention to the most susceptible women during the seasons of high malaria exposure.

Adolescent↗
PubMed1996

The effect of malaria and malaria prevention in pregnancy on offspring birthweight, prematurity, and intrauterine growth retardation in rural Malawi.

While there is broad evidence for the adverse effects of Plasmodium falciparum infection in pregnancy, and the World Health Organization recommends preventive strategies, there is markedly reduced efficacy in sub-Saharan Africa of the most widely available, affordable and used antimalarial drug for chemoprophylaxis-chloroquine (CQ). During 1987-1990, we studied pregnant women in an area of high malaria endemicity in rural Malawi to compare the efficacy of CQ (the drug recommended by national policy) with mefloquine (MQ, a relatively new and highly effective antimalarial) in preventing low birth weight (LBW) due to prematurity and intrauterine growth retardation (IUGR). Among 1,766 women monitored during at least their last six weeks of pregnancy with observed ingestion of their regimen and facility delivery of a live born singleton, their babies had a mean +/- SD birth weight of 2,905 +/- 461 gm and 16.8% had LBW. In a multivariate analysis, factors significantly associated with LBW included: first birth (odds ratio [OR] = 4.27), female infant (OR = 2.92), maternal human immunodeficiency virus infection (OR = 2.66), low maternal weight (OR = 1.95), and placental blood P. falciparum infection (OR = 1.71). Factors significantly associated with IUGR-LBW included first birth, female infant, low maternal weight, and placental malaria. Factors significantly associated with preterm-LBW included maternal syphilis infection, umbilical cord blood malaria, first birth, low maternal weight, and female infant. Use of an effective antimalarial (MQ) was protective against LBW through its effect on reducing placental and umbilical cord blood malaria infection. The proportion of LBW babies born to women on MQ (12.5% [parity-adjusted for the population of delivering women]) was significantly lower than the proportion born to women on CQ (15.5%; P = 0.05). Effective prevention of malaria in pregnant women in malaria-endemic settings may reduce the likelihood of LBW by 5-14%, and may reduce the amount of preventable LBW by more than 30%. When evaluating antenatal care programs, health policy makers must consider providing an effective preventive drug (either MQ or other drugs identified in additional studies, e.g., sulfa-pyrimethamine compounds) as a means to prevent low birth weight and its consequences.

Adolescent↗
PubMed1996

Malaria treatment and prevention in pregnancy: indications for use and adverse events associated with use of chloroquine or mefloquine.

In sub-Saharan Africa, women frequently report a variety of symptoms during pregnancy, some of which indicate possible illness. Given the adverse impact of malaria in pregnancy, these events may be important for at least two reasons: it may be possible to use reported fever illness as a determinant of which women need an antimalarial intervention, and, it is possible that adverse symptoms following the antimalarial intervention may be important determinants of continued adherence to the prevention regimen. In a cohort of pregnant women enrolled at first antenatal clinic visit in rural Malawi, we evaluated reported fever, determined parasitemia, and placed the women on antimalarial regimens containing chloroquine (CQ) or mefloquine (MQ). We then systematically evaluated reported symptoms following antimalarial drug use after initial therapeutic doses and subsequent prophylactic doses, and monitored women throughout their pregnancy and at delivery. Among 4,187 enrolled women, 1,048 (25%) reported at least one febrile episode during pregnancy before their first antenatal clinic visit. Factors associated with this reported fever included low parity, enrollment in the rainy season, human immunodeficiency virus seropositivity, use of antimalarial prophylaxis before enrollment, high socioeconomic status, normal (compared to low) maternal height and weight, and literacy. Fever before the first antenatal clinic visit was reported by 24.4% of parasitemic women and 25.4% of aparasitemic women; the sensitivity and specificity of fever to identify parasitemic women was 24% and 71%, respectively. In contrast, the sensitivity and specificity of first or second pregnancy to identify parasitemic women was 71% and 57%, respectively. Among women on a CQ or MQ regimen, approximately 60% reported side effects (e.g., itching, dizziness, and gastrointestinal disturbances) after a treatment dose and approximately 25% reported side effects after a prophylactic dose; rates and types of symptoms reported were similar in the CQ and MQ groups. Few serious side effects were observed and rates of fetal loss were low and similar in the groups. Reliance on fever illness will be wholly inadequate to identify parasitemic women; therefore, our findings support existing World Health Organization recommendations that presumptive treatment and prevention regimens should be offered to all pregnant women. When resources are inadequate to offer antimalarial prophylaxis to all pregnant women, women in their first or second pregnancy may be a more appropriate target group than pregnant women with reported fever. Education regarding expected minor side effects may reduce rates of poor compliance and improve the effectiveness of the prevention effort.

Adolescent↗
PubMed1996

Transplacental transmission of Plasmodium falciparum in rural Malawi.

Malaria during pregnancy may result in fetal exposure to malaria when parasites are transmitted across the placenta. To document the rate of transplacental passage of Plasmodium falciparum and to identify the risk factors for congenitally acquired malaria infection, we examined umbilical cord blood for malaria parasites from 2,080 newborn infants born to mothers enrolled in a study of malaria prophylaxis during pregnancy. Cord blood parasitemia was detected in 140 (6.7%) newborn infants with a geometric mean density of 187 parasites/microliter (range 12-99, 752 parasites/microliter). The likelihood of umbilical cord blood parasitemia was closely linked to the parasite density of placental malaria infection and the density of maternal peripheral blood parasitemia at the time of delivery; all babies born to women with both placental and peripheral blood parasitemia densities > or = 10,000/microliter had cord blood parasitemia. In a multivariate logistic regression model, male sex, premature delivery, and placental and maternal peripheral blood malaria parasitemia were independently associated with a baby being born with umbilical cord blood parasitemia. In this setting, highly endemic for malaria, transplacental transmission of malaria from infected placentae occurs frequently and is directly related to the density of maternal malaria infection.

Adolescent↗
PubMed1996

The effect of placental malaria infection on perinatal mortality in rural Malawi.

Perinatal deaths (fetal or infant deaths from the 28th week of pregnancy up to the seventh day after birth) occur as a result of adverse conditions during pregnancy, labor, and delivery, or in the first few days of life. Placental malaria infection is known to increase the risk of delivery of a low birth weight infant, thus, potentially increasing the risk of perinatal and infant mortality. To better understand the relationship among the adverse events in pregnancy, including placental malaria infection, adverse conditions in labor, and birth weight to perinatal mortality, we investigated the perinatal mortality among a cohort of infants born to rural Malawian women for whom placental malaria infection status and birth weight were documented. Among the 2,063 mother-singleton infant pairs, there were 111 perinatal deaths (53.8 perinatal deaths per 1,000 births). The risk of perinatal death increased as birth weight decreased. Risk factors identified for perinatal mortality among all infants excluding birth weight included abnormal delivery (cesarean section, breech, or vacuum extraction), a history of a late fetal or neonatal death in the most recent previous birth among multiparous women, reactive maternal syphilis serology, nulliparity, and low socioeconomic status. Placental malaria infection was not associated with increased perinatal mortality, but was associated with lower perinatal mortality among normal birth weight (> or = 2,500 g) infants (odds ratio = 0.35, 95% confidence interval = 0.14, 0.92). Interventions to address these risk factors could have a substantial impact on reducing perinatal mortality in this population.

Adolescent↗
PubMed1996

Prospective assessment of mortality among a cohort of pregnant women in rural Malawi.

Maternal mortality has recently received attention as a neglected public health problem in many developing countries where mortality rates are estimated to be 8-200 times those in developed countries. Most maternal mortality estimates in sub-Saharan Africa have used retrospective methods because of the lack of large population-based studies. The Mangochi Malaria Research Project, a trial of antimalarial chemoprophylaxis in pregnant women, provided an opportunity to examine prospectively mortality among the study women. Among 4,053 monitored pregnant women, 27 women were known to have died during pregnancy, labor, delivery and the one-year follow-up period. Three women died during the antenatal period and 12 died within six weeks of delivery for an estimated maternal mortality rate of 370 per 100,000 pregnant women; this rate was consistent with rates reported from retrospective surveys in Malawi. Twelve women died between three and 10 months after delivery, and the mortality rate in this nonmaternal period was estimated to be 341 per 100,000. Mortality rates in the maternal and nonmaternal periods were surprisingly similar. Human immunodeficiency virus type-1 (HIV-1) infection and anemia were strongly associated with death in the nonmaternal period. Mortality among infants of mothers who died was 3.7 times higher than the rate of death among infants born to mothers who survived. This study highlights that for rural Malawian women, pregnancy and delivery are risky periods, that the death of the mother adversely affects the survival of her children, and that HIV and anemia are important contributors to nonmaternal mortality in reproductive-age women. Strategies to reduce mortality among women of child-bearing age in sub-Saharan Africa must focus on decreasing the complications of pregnancy and delivery, and address important preventable causes of death, such as anemia and HIV infection.

Cause of Death↗
PubMed1996

Malaria infection in infancy in rural Malawi.

Malaria infection is thought to be relatively infrequent in infants less than 90 days of age in sub-Saharan Africa. In a rural area of Malawi with intense malaria transmission, we examined the occurrence of malaria infection during infancy and risk factors for parasitemia in the first three months of life in the cohort of infants delivered to women in the Mangochi Malaria Research Project. Among 3,915 liveborn singleton infants, 3,432 (87.7%) were seen at least once during infancy (first 12 months of life); of these, malaria blood smear results were available on 2,649 (77.2%). Overall, in a cross-sectional analysis, 23.3% of infants at three months of age were infected with Plasmodium falciparum; this proportion increased to more than 30% during the high transmission season. By the age of 10 months, 60-80% of the infants were infected, depending on the season. Geometric mean parasite density increased each month after two months of age and plateaued at seven months of age. In a life-table analysis, the median time to acquisition of a positive smear was 199 days. Factors independently associated with smear positivity at < 4 months of age included visit during high transmission season (adjusted odds ratio [AOR] = 4.1), maternal smear positivity at the same visit (AOR = 3.5), history of infant fever in the previous two weeks (AOR = 2.8), birth during the rainy season (AOR = 1.7), low socioeconomic status (AOR = 1.6), and low maternal education (AOR = 1.5). The specificity of a recent fever history for malaria infection in early infancy was high (> 70%). Intervention strategies to reduce the risk of early infant infection need to be targeted toward mothers of infants at high risk.

Age Factors↗
PubMed1996

Infant and second-year mortality in rural Malawi: causes and descriptive epidemiology.

Community information based on causes and circumstances of death in infants and young children in Malawi was obtained in a prospective cohort of babies delivered to women enrolled in a malaria-prevention-in-pregnancy study. Vital status information was obtained through home visits every two months; for children who died, questions were asked concerning age and date of death, symptoms preceding death, care sought, location of death (home versus facility), and duration of illness. Of 3,274 liveborn singleton infants, 181, 397, and 152 deaths occurred in the neonatal, postneonatal, and second year of life, respectively. For neonates, proportionate mortality was greatest for sepsis/tetanus (16.7%) and fever (8.6%); however, for more than half of neonatal deaths evaluated the cause was not identified. Up to 30% of neonatal deaths may have been related to prematurity. In the postneonatal period, gastrointestinal illness (39.6%), fever (18.3%), and respiratory illness (14.7%) were the leading causes. Most postneonatal illnesses lasted 1 week or less. Two-thirds of postneonatal deaths occurred outside of a health care facility, although 80% were brought to a facility for care during their illness. Infectious disease syndromes continued to be important in the second year of life, with gastrointestinal (31.6%), fever (23.5%), and measles (20.6%) the most commonly reported causes of death. In this area of rural sub-Saharan Africa, neonatal mortality contributes substantially to infant mortality, and prematurity is considered to be an important component of early neonatal deaths; infectious disease syndromes predominate in the postneonatal and second year of life. Strategies to reduce infant deaths in sub-Saharan Africa must consider these factors, as well as the observations that most children who died had brief illnesses, were taken to a health care facility before death, yet died at home.

Age Factors↗
PubMed1996

Objectives and methodology in a study of malaria treatment and prevention in pregnancy in rural Malawi: The Mangochi Malaria Research Project.

Malaria infection due to Plasmodium falciparum has been widely recognized as associated with important adverse consequences in pregnant women, particularly in areas of high transmission. Although strategies using antimalarial drugs for prevention had been recommended, even by the late 1980s, few studies had been carried out to examine the efficacy of these prevention efforts. The objectives of the Mangochi Malaria Research Project investigation were to determine the comparative efficacy of regimens containing chloroquine (CQ) or mefloquine (MQ) antimalarial treatment and chemoprophylaxis in an area of CQ-resistant P. falciparum on the following outcomes: 1) the frequency of placental malaria infection; 2) the frequency of low birth weight; 3) the frequency of prematurity or intrauterine growth retardation; 4) the frequency of maternal fever illness and severe anemia; and 5) the likelihood of infant acquisition of malaria infection. Although the investigation was not designed to evaluate the role of antimalarial chemoprophylaxis and treatment on infant mortality reduction, because babies born to study women were scheduled to be followed for up to two years of life, the study allowed for an examination of mortality and morbidity in this population. The sample size was insufficient to provide more than descriptive analysis of mortality and morbidity in the fetal, perinatal, neonatal, postneonatal, and infant time intervals. The study design allowed for the evaluation of two additional aspects of maternal and infant health: other determinants of the above-listed outcomes in addition to malaria prevention (e.g., maternal age, gravidity, socioeconomic status, infection with human immunodeficiency virus or syphilis) and reported cause-specific mortality in the fetal-to-infant intervals. The study design included 22 months of enrollment of pregnant women at their first antenatal clinic visit from four clinic sites in Mangochi District, Malawi, with assignment to one of four antimalarial regimens and prospective follow-up through pregnancy, at delivery, and during infancy. All drug dosing was performed under supervision by the study team, making this an evaluation of intervention efficacy (excluding the role of patient compliance).

Antimalarials↗
PubMed1996

Rates and risk factors for mortality during the first two years of life in rural Malawi.

Developing nations in sub-Saharan Africa experience childhood mortality rates that are much higher than any other region of the world. In a rural Malawian community we investigated risk factors for deaths occurring during the neonatal (birth-28 days), postneonatal (29-365 days), infant (birth-365 days), and second-year (366-730 days) periods among a cohort of 3,724 infants monitored from birth. The neonatal mortality rate in this cohort was 48.6 per 1,000 live births (LB); the postneonatal mortality rate was 108.7/1,000 LB. The overall infant mortality rate was 157.3 deaths/1,000 LB and the mortality rate for the first two years of life was 223.7 deaths/1,000 LB. The predominate risk factors for neonatal deaths identified in multivariate analysis were low (hazard ratio [HR] = 2.3) and very low birth weight (HR = 12.7), first pregnancy (HR = 1.8) and maternal syphilis infection (HR = 2.4). Maternal infection with human immunodeficiency virus (HIV) (HR = 1.5) predominated for postneonatal deaths. Low (HR = 1.4) and very low (HR = 5.0) birth weight, first pregnancy (HR = 1.6), maternal HIV infection (HR = 2.4), and the combination of low education and low socioeconomic status (SES) of the mother (HR = 2.0) were the most important factors during the infant period. Maternal HIV infection (HR = 3.3) and the combination of low education and low SES of the mother (HR = 2.6) were the predominate risk factors for mortality occurring during the second year. Factors that were significant in univariate analysis but not significant in the final multivariate models included prematurity, previous adverse reproductive outcome, dying during high malaria transmission season, and being born at home. Interventions to prevent maternal HIV infection and low birth weight and treatment of syphilis infection would have a great impact on reducing early childhood deaths. Improving the delivery of health care and education to women during their first pregnancy and to the most socially disadvantaged women may also help reduce the burden of early childhood mortality in communities such as the one studied in Malawi.

Cohort Studies↗
PubMed1994

Strategies for laboratory HIV testing: an examination of alternative approaches not requiring Western blot.

Advances in laboratory tests for antibodies to human immunodeficiency virus (HIV) have permitted the development of alternative HIV testing strategies that do not require use of the Western blot approach. Three strategies are proposed. In strategy I, sera are tested for HIV antibody using an enzyme-linked immunosorbent assay (ELISA)/rapid/simple (ERS) test; in strategy II, sera reactive in an initial ERS test are retested using a second ERS test; strategy III involves retesting with a third ERS test all sera reactive in two previous ERS tests. Where the objective is identification of asymptomatic HIV-infected individuals, strategy III is proposed where HIV prevalences in the study population are < or = 10%, and strategy II at prevalences > 10%. Strategy II is recommended where the diagnosis of HIV-related disease requires HIV testing. For serosurveillance, strategy II is recommended if the prevalence is < or = 10%, and strategy I if the prevalences are > 10%. Use of strategy I is recommended for transfusion and transplantation safety, at any prevalence. Lower-cost laboratory HIV testing will permit such testing to become more widely available.

AIDS Serodiagnosis↗
PubMed1993

Risk factors for HIV infection among abandoned Romanian children.

OBJECTIVE: To determine risk factors for HIV infection among abandoned Romanian infants and children living in a public institution. METHODS: A cross-sectional study was conducted in June 1990 among 101 children between 0 and 4 years of age living in an orphanage. Orphanage and hospital records were reviewed and a blood specimen for hepatitis B and HIV serologic testing obtained from each child. A case-control study was conducted using data from the cross-sectional study. Cases were HIV-positive children; one HIV-negative control, matched by age, was selected for each case. RESULTS: Overall, 20 (20%) children were HIV-positive, 88 (87%) tested positive for antibody to hepatitis B core antigen, and 32 (32%) were hepatitis B surface antigen-positive. In the case-control study, HIV-positive children had received more therapeutic injections [mean, 280; median, 231] than age-matched HIV-negative children [mean; 142, median, 155; P = 0.02]. Cases were more likely than controls to have received over 200 lifetime injections (odds ratio, 5.7; 95% confidence interval, 1.2-32.7). Blood transfusions and mother-to-child transmission were excluded as routes of HIV transmission. By reviewing sterilization records and interviewing local health-care workers, we determined that needles and syringes were often re-used without proper disinfection in the orphanage. CONCLUSIONS: These data provide strong epidemiologic evidence that indiscriminate injections with contaminated needles and syringes were responsible for HIV transmission in this population.

Blood Transfusion↗