Maternal HIV infection and infant mortality in Malawi: evidence for increased mortality due to placental malaria infection.

OBJECTIVES: To examine the relationship between maternal HIV infection, placental malaria infection, and infant mortality as a first step in investigating the possibility of increased vertical transmission of HIV due to placental malaria infection. DESIGN: Retrospective analysis of data from a cohort study of mothers and infants in rural Malawi conducted from 1987 to 1990. METHODS: Pregnant women in Malawi were enrolled in a study examining chemoprophylaxis during pregnancy. At delivery, placental malaria infection status was determined. Infants born into this study were visited every 2 months for the first 2-3 years of life. Deaths were investigated using a standardized 'verbal autopsy' interview. Maternal serum collected during pregnancy was tested for antibodies to HIV-1 by enzyme-linked immunosorbent assay with Western blot confirmation. RESULTS: Overall, 138 (5.3%) of 2608 women in the study were HIV-1-seropositive. Infant mortality rates were 144 and 235 per 1000 live births for children born to HIV-seronegative and HIV-seropositive women, respectively (P < 0.001). In a multivariate model, the odds of dying during the post-neonatal period for an infant born to a mother with both placental malaria and HIV infection was 4.5 times greater than an infant born to a mother with only placental malaria, and between 2.7 and 7.7 times greater (depending on birthweight) than an infant born to a mother with only HIV infection. CONCLUSIONS: This study strongly suggests that exposure to both placental malaria infection and maternal HIV infection increases post-neonatal mortality beyond the independent risk associated with exposure to either maternal HIV or placental malaria infection. If confirmed, malaria chemoprophylaxis during pregnancy could decrease the impact of transmission of HIV from mother to infant.

PIP: Researchers analyzed data on 2608 women attending one of four prenatal clinics in Mangochi District in Malawi during 1987-1990 to study the relationship between maternal HIV infection, placental malaria infection, and infant mortality. 5.8% (138) of the women were HIV-1 seropositive. HIV-1 seroprevalence increased from 2.3% to 5.8% between 1987 and 1993. Infants born to HIV-1 positive mothers were much more likely to die during the first year of life than those born to HIV-1 negative mothers (235/1000 vs. 144/1000 live births; p 0.001). The excess deaths occurred during the postneonatal period (49 vs. 44, p = 0.3, for neonatal mortality, compared to 186 vs. 100, p 0.001, for postneonatal mortality). In the postneonatal period, diarrhea or gastrointestinal illness was more common as a cause of death among infants of HIV-1 positive mothers than those of HIV-1 negative mothers (8.7% vs. 3.6%; relative risk = 2.4; p = 0.0002). The researchers stratified the effect of maternal HIV infection on postneonatal death according to birth weight and placental malaria infection to control for potential confounding. They found that, when compared with normal birth weight infants born to seronegative mothers with no placental malaria infection, low birth weight infants born to HIV-1 positive mothers with placental malaria had an 11.49 increased odds of dying during the postneonatal period. The multivariate analysis showed that an infant born to an HIV-infected mother with placental malaria was 4.5 times more likely to die during the first year of life than an infant born to a mother with only placental malaria and 2.7-7.7 times (depending on birth weight) more likely to die than an infant born to a mother with only HIV infection. These findings suggest that malaria chemoprophylaxis during pregnancy would reduce the likelihood of HIV transmission from mother to infant in addition to reducing the burden of malaria infection during pregnancy, malaria-associated low birth weight, and their subsequent effect on child survival.

Trends and risk factors for HIV-1 seropositivity among outpatient children, Kinshasa, Zaire.

To investigate recent trends in pediatric HIV-1 infection and the early impact of a blood screening program begun in one hospital in 1987 in Kinshasa, Zaire, we evaluated 1110 consecutive children seen in the pediatric emergency ward of the city's largest hospital in November 1988. The HIV-1 seroprevalence was 5.0%, not significantly higher than the rate of 3.8% found in 1986 (P = 0.2). The seropositivity rate was bimodally distributed; children less than 6 months of age had a higher rate (12.6%) than children 6-11 months old (1.9%; OR = 7.6; P less than 0.0001) and children 1-13 years old (4.1%; OR = 3.4; P less than 0.0001). Seropositive children greater than or equal to 1 year of age were more likely than seronegative children to be anemic and to have signs of malnutrition. A previous blood transfusion was associated with HIV-1 seropositivity among children greater than or equal to 1 year of age (OR = 5.4, P less than 0.0005), but not among younger children. Fifty-two per cent of seropositive children greater than or equal to 1 year of age received a transfusion (etiological fraction = 42%). The association with seropositivity was higher for those who had received a transfusion before 1987 than for those who had received a transfusion since 1987 (OR = 4.8, P = 0.01). These findings suggest a relatively stable, high pediatric HIV-1 seroprevalence in Kinshasa and a decreased but continued risk of transfusions. Expansion of currently limited blood transfusion screening programs, and the development of new strategies for limiting transfusions and preventing severe anemia, are needed.

PIP: To investigate recent trends in pediatric HIV-1 infection and the early impact of a blood screening program begun in 1 hospital in Kinshasa, Zaire, the authors evaluated 1110 consecutive children seen in the pediatric emergency ward of the city's largest hospital in November 1988. The HIV-1 seroprevalence was 5.0%, not significantly higher than the 3.8% rate found in 1986 (p=0.2). The seropositivity rate was bimodally distributed; children 6 months of age had a higher rate (12.6%) than children 6-11 months old (1.9%; OR+7.6; p0.0001) and children 1-13 years old (4.1%; OR+3.4; p0.0001). Seropositive children or= 1 year of age were more likely than seronegative children to be anemic and to have signs of malnutrition. A previous blood transfusion was associated with HIV-1 seropositivity among children or= 1 year of age (OR=5.4, p0.0005), but not among younger children. 52% of seropositive children or= 1 year of age had received a transfusion (etiological fraction=42%). The association with seropositivity was higher for those who had received a transfusion before 1987 than for those who received 1 since that time (OR=4.8, p=0.01). These findings suggest a relatively stable, high pediatric HIV-1 seroprevalence in Kinshasa and a decreased but continuous risk of transfusions. Expansion of currently limited blood transfusion screening programs and the development of new strategies for limiting transfusions and anemia prevention are necessary.

Treatment of chloroquine-resistant malaria in African children: a cost-effectiveness analysis.

Because chloroquine (Cq)-resistant Plasmodium falciparum (CRPF) has now spread throughout most of Africa, the efficacy and practicability of other drugs such as amodiaquine (Aq), and pyrimethamine-sulfadoxine (PS), for the treatment of fever needs to be assessed. We used a decision-analysis model to compare the cost and effectiveness of Cq, Aq, and PS. The variables considered were the probability of P. falciparum infection, drug compliance, minor and lethal side effects of the drug, the level of drug resistance in the community, and case-fatality rates associated with treatment. The measures of effectiveness were the number of malaria-related fever episodes cured parasitologically with each treatment and the number of malaria deaths prevented in children 6-59 months old. Cost-effectiveness comparisons were made for cases cured and deaths prevented. For treating 100,000 febrile episodes, Cq, PS, and Aq cost US$1812, US$2622, and US$3044, respectively. Cost of the drug, compliance, and the level of CRPF had the greatest effect on the cost-effectiveness ratio. The prevalence of high-level drug resistance (RIII) was the most important determinant of the cost-effectiveness. In a scenario with high-level CRPF, treatment with Cq costs US$0.47 to cure one patient and US$2.29 to prevent one death compared with US$0.05 and US$1.52 for treatment with PS. When the prevalence of RIII-level CRPF is greater than 14-31% (depending on the level of compliance), the most cost-effective treatment is PS, despite its 45% greater cost. Decision analysis models will be useful for malaria control planners as strategies are reconsidered in the 1990s.

The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden.

Malarious patients experience asymptomatic parasitemia; acute febrile illness (with cerebral damage, anemia, respiratory distress, hypoglycemia); chronic debilitation (anemia, malnutrition, nervous system-related sequelae); and complications of pregnancy (anemia, low birth weight, increased infant mortality). These manifestations in patients, communities, and countries reflect intrinsic (human, parasite, mosquito) and extrinsic (environmental, social, behavioral, political, and economic conditions as well as disease-control efforts) determinants. At a minimum, between 700,000 and 2.7 million persons die yearly from malaria, over 75% of them African children. Between 400 and 900 million acute febrile episodes occur yearly in African children under 5 yr of age living in endemic areas. Although about half of these children are parasitemic, all merit consideration of malaria-specific therapy, which is becoming more problematic because of parasite resistance to drugs. These numbers will more than double over the next 20 yr without effective control. Fewer than 20% of these febrile episodes and deaths come to the attention of any formal health system. The relatively few ill patients who have any contact with the health services represent the "ears of the hippopotamus." Greatly intensified research activities and control of the intolerable burden of malaria are mandatory if economic development is to accelerate in Africa. In particular, support should be targeted to understanding and preventing malaria-induced anemia, hypoglycemia, effects on pregnancy, and neurologic and developmental impairment. To decrease and stop transmission of this intolerable scourge, there is an urgent need for malaria vaccines, newer drugs, and better vector control methods as well as the ability to improve current technologies and use them more efficiently.

Gaps in the childhood malaria burden in Africa: cerebral malaria, neurological sequelae, anemia, respiratory distress, hypoglycemia, and complications of pregnancy.

Evaluations of the African childhood malaria burden do not fully quantify the contributions of cerebral malaria (CM), CM-associated neurological sequelae, malarial anemia, respiratory distress, hypoglycemia, and pregnancy-related complications. We estimated the impact of these malaria manifestations on members of the African population < 5 years old. Calculations were based on an extensive literature review that used National Library of Medicine search engines, other bibliographic sources, and demographic data. In sub-Saharan Africa, CM annually affects 575,000 children < 5 years of age and 110,000 (approximately 19% case fatality rate [CFR]) die. Childhood survivor, of CM experience developmental and behavioral impairments: each year, 9,000-19,000 children (> 2% of survivors of CM) < 5 years of age in Africa experience neurological complications lasting > 6 months. Severe malarial anemia heavily burdens hospitals with rising admission and CFRs and with treatments that are complicated by limited and sometimes contaminated blood supplies. Severe malarial anemia occurs 1.42-5.66 million times annually and kills 190,000-974,000 (> 13% CFR) children < 5 years of age annually. Respiratory distress, hypoglycemia, and overlapping clinical manifestations cause 1.12-1.99 million cases and > 225,000 (> 18% CFR) additional deaths among African children with malaria. Maternal, placental, or fetal malaria infection during pregnancy adversely affects development and survival of fetuses and newborns through low birth weight (LBW), maternal anemia, and possibly abortion and stillbirth. Between 167,000 and 967,000 cases of malaria-associated LBW occur yearly; malaria-induced LBW kills 62,000-363,000 (> 38% CFR) newborns each year. All the gaps in the burden comprise 0.4-1.7 million deaths annually, > 50% of which are due to severe malarial anemia. These malaria-induced medical problems constitute major clinical, public health, and research challenges in that they may contribute to more than double the mortality than is generally acknowledged.

Malarial antibodies measured by the indirect hemagglutination test in West African children.

The indirect hemagglutination test with Plasmodium falciparum antigen was used to measure malarial antibodies in filter paper blood specimens from 527 West African children. A slight decline in antibodies was noted in 6- to 8-month-old children wh o had no malaria parasites in their blood smears. Children older than 10 months had similar antibody levels regardless of the presence or absence of demonstrated parasites in blood smears.

Chloroquine-resistant falciparum malaria in northern Malawi.

An American Peace Corps volunteer contracted chloroquine-resistant Plasmodium falciparum malaria while serving in Malawi and taking regular chloroquine prophylaxis. Resistance was confirmed by in vitro testing of his parasites for chloroquine and pyrimethamine. The possibility of Fansidar-resistant falciparum malaria was also suggested in this case. American expatriates residing in or traveling to Malawi are advised to either take both chloroquine and Fansidar, or alternatively amodiaquine or doxycycline alone. Any breakthrough of slide-proven falciparum malaria in these individuals should be seriously suspected to be chloroquine- and Fansidar-resistant malaria, and should be treated with quinine and tetracycline.

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.

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.

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.

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.

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.

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.

Smallpox in the Republic of Guinea, West Africa. II. Eradication using mobile teams.

Smallpox transmission was interrupted in the Republic of Guinea in January 1969, 13 months after the beginning of the National Smallpox Eradication Program, and after approximately 60% of the population had been mass vaccinated. The eradication strategy was founded on the recent epidemiology of smallpox in Guinea and surrounding countries. Tactics were based on use of mobile teams specifically trained for mass vaccination, assessment, surveillance, and epidemic investigation. Guinea was one of 15 West African countries officially certified by the World Health Organization in 1976 as having eradicated smallpox. Continued vigilance to detect any possible importation is needed and would best be part of a program to improve quarantinable disease surveillance. An acceptable immunity level to smallpox should be maintained in priority groups until worldwide smallpox eradication is achieved.

Human poxvirus disease after smallpox eradication.

A 5-year-old boy living in a small camp in the rural Ivory Coast had a disease resembling smallpox. This occurred 4 years after smallpox had been eradicated from the Ivory Coast and 1.5 years after the last case of smallpox was detected in West and Central Africa. Clinical, serological, and epidemiological evidence indicated this disease was probably monkeypox, a poxvirus of the variola/vaccina subgroup. A serologic survey of poxvirus antibodies in the wild animal population detected neutralizing antibodies in rodents, larger mammals, primates, and birds. The laboratory and ecological characteristics of poxviruses require further elucidation, especially those which have been found in animals near human monkeypox cases.

The effectiveness of insecticide-impregnated bed nets in reducing cases of malaria infection: a meta-analysis of published results.

The use of insecticide-impregnated bed nets to minimize human-vector contact may reduce the incidence of malaria. Consequently, several field trials have evaluated their effectiveness as a malaria prevention strategy. A meta-analysis of published reports of field trials that measured the incidence of infections was performed to provide a measure of the effectiveness of insecticide-treated bed nets in preventing clinical malaria. Subsetted analyses were performed on the 10 field trials to calculate pooled incidence rate ratios of infection among the study groups. For the studies comparing insecticide-impregnated bed nets with untreated bed nets, the summary incidence rate ratio for acquiring malarial infections was 0.757 (95% confidence interval [CI] = 0.612-0.938), representing a reduction of 24%. For the studies comparing permethrin-impregnated bed nets with controls without bed nets, the summary incidence rate ratio was 0.497 (95% CI = 0.417-0.592) (Rothman-Boice heterogeneity statistics = 17.27 [P = 0.004] and 23.55 [P = 0.0003], respectively). These data suggest that insecticide-impregnated bed nets are effective in preventing malaria, decreasing the incidence rate ratio by approximately 50% in field trials performed to date.

Permethrin-impregnated curtains and bed-nets prevent malaria in western Kenya.

The effectiveness of permethrin-impregnated (0.5 g/m2) bed-nets and curtains as malaria control measures was evaluated in Uriri, Kenya in 1988. One hundred five families were randomly assigned to 1 of 3 study groups (control, bed-net, or curtain). All participants were cured of parasitemia with pyrimethamine/sulfadoxine. Selective epidemiologic and entomologic parameters were measured weekly, while knowledge, attitude, and practices surveys were conducted at the beginning and end of the 15 week study. Plasmodium falciparum infections per person week at risk were significantly higher in the control group than in either the curtain group (5.42 vs. 2.35 cases/100 person weeks risk) or the bed-net group (5.42 vs. 3.77 cases/100 person weeks risk). The curtain group had fewer infections per person week at risk than the bed-net group (2.35 vs. 3.77 cases/100 person weeks risk). A difference was found in clinical malaria among the groups: 45% of persons in the bed-net and curtain groups vs. 30% of those in the control group reported no episodes of fever and chills (chi 2, P less than 0.05). Indoor resting Anopheles gambiae or An. funestus were found on 94 occasions in the control houses, but only twice in the treated houses during weekly visits to each house over the study period (chi 2 P less than 0.001). The pyrethrum knockdown method produced similar results with a total of 195, 23, and 3 An. gambiae and An. funestus collected in the control, bed-net, and curtain houses during the same period, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effectiveness of permethrin-impregnated bed nets and curtains for malaria control in a holoendemic area of western Kenya.

The effectiveness of village-wide use of permethrin-impregnated bed nets or eave, window, and door curtains as control measures for Plasmodium falciparum malaria was evaluated during two successive high-transmission seasons in western Kenya. Pairs of villages were assigned to one of three study groups: bed net, curtain, or control. Clinical, parasitologic, and entomologic measures were made from March to July 1990 and again 12 months later. When compared with the controls in 1990 and 1991, we observed a marked reduction in the incidence of P. falciparum infections in children less than six years old in the bed net villages (reduced by 40% and 48%) and a smaller but still significant reduction in the curtain villages (10% and 33%). Significant reductions were also seen in the incidence of P. falciparum parasitemias greater than 2,500/mm3 in the bed net group (reduced by 44% and 49%) and curtain group (16% and 32%). Additionally, we observed significant reductions in the incidence of documented fevers in association with P. falciparum parasitemia in bed net (reduced by 63%) and curtain villages (53%) when compared with controls. Entomologic inoculation rates in both bed net and control villages decreased by more than 50% below control values during both high transmission seasons. The results of this study, together with a 1988 study in the same area during the low transmission season, show that bed nets offer greater year-round of protection against P. falciparum infection than curtains. However, during the high transmission season, this technique reduces the frequency of P. falciparum infection rather than preventing it entirely.

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.

PIP: During September 1987 to June 1990, 3380 pregnant women with parasitemia attending 4 prenatal care clinics in rural Mangochi District, Malawi, were assigned to 1 of 4 regimens of antimalarial treatment and/or prophylaxis. The women were followed through delivery to determine the antimalarial drug efficacy on peripheral parasitemia during pregnancy and parasitemia at the time of delivery in peripheral, placental, and umbilical cord blood. The regimens were 3 regimens for chloroquine (CQ), 1 of which was the current standard of care in Malawi, and a mefloquine (MQ) regimen. Parasite clearance was not achieved in 18.4% of the 1528 women with parasitemia at enrollment. 17.3% of the 1852 women who were aparasitemic at enrollment had breakthrough infections. Women using a CQ regimen faced a significantly greater risk of persistent and breakthrough parasitemia (odds ratio [OR ] = 30.9 and 11.1, respectively; p 0.0000001). The multivariate analysis found other significant risk factors for malaria to be first pregnancy (OR = 3.6 for persistent malaria and 1.5 for breakthrough malaria), enrollment in the rainy or post-rainy season (OR = 2-3.4 for persistent parasitemia and 1.2-2.7 for breakthrough malaria), maternal age of at most 25 years (OR = 2.3 for persistent malaria and 1.6 for breakthrough malaria), and seropositivity to HIV (OR = 1.9 for persistent malaria). At delivery, women on a CQ regimen faced a significantly higher risk of peripheral, placental, or umbilical cord parasitemia than those using MQ (OR = 8.7, 7.4, and 4.1, respectively; p 0.000001). In the multivariate model, other significant risk factors for malaria at delivery were first pregnancy, enrollment in the rainy or post-rainy season, maternal age of at most 25 years, and seropositivity to HIV. The most important determinant of falciparum malaria in pregnant women was use of an ineffective intervention (i.e., CQ in an area with CQ-resistant parasites). Based on these findings, the researchers recommend that antimalarial programs focus on highly efficacious drugs and targeting pregnant women during the season of high malaria exposure.

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.