Drug dispensing practices during implementation of artemisinin-based combination therapy at health facilities in rural Tanzania, 2002-2005.

OBJECTIVE: To assess the degree to which policy changes to artemisinin-based combination therapies (ACTs) as first-line treatment for uncomplicated malaria translate into effective ACT delivery. METHODS: Prospective observational study of drug dispensing practices at baseline and during the 3 years following introduction of ACT with sulfadoxine-pyrimethamine (SP) plus artesunate (AS) in Rufiji District, compared with two neighbouring districts where SP monotherapy remained the first-line treatment, was carried out. Demographic and dispensing data were collected from all patients at the dispensing units of selected facilities for 1 month per quarter, documenting a total of 271, 953 patient encounters in the three districts. RESULTS: In Rufiji, the proportion of patients who received a clinical diagnosis of malaria increased from 47.6% to 57.0%. A majority (75.9%) of these received SP + AS during the intervention period. Of patients who received SP + AS, 94.6% received the correct dose of both. Among patients in Rufiji who received SP, 14.2% received SP monotherapy, and among patients who received AS, 0.3% received AS monotherapy. CONCLUSIONS: The uptake of SP + AS in Rufiji was rapid and sustained. Although some SP monotherapy occurred, AS monotherapy was rare, and most received the correct dose of both drugs. These results suggest that implementation of an artemisinin combination therapy, accompanied by training, job aids and assistance in stock management, can rapidly increase access to effective antimalarial treatment.

The incidence of clinical malaria detected by active case detection in children in Ifakara, southern Tanzania.

Between July 2000 and June 2001, we used weekly active case detection (ACD) of clinical malaria episodes in 618 children aged < 5 years to describe the epidemiology of malaria in Ifakara, southern Tanzania. Plasmodium falciparum-positive blood slides prepared from children with axillary temperature 37.5 degrees C were used to define clinical malaria and a rolling cross-sectional survey documented the prevalences of parasitaemia and anaemia. A random subsample of children was visited daily for 1 month at the end of the study to assess the effect of more frequent visits on estimated incidence rates. Only 50 (8%) children had 1 or more episodes of clinical malaria during the year, an overall incidence of 0.275 episodes/100 child-weeks-at-risk, with no age dependence. The maximum parasite prevalence of 25% was reached in children aged 4 years. The incidence of illness was significantly lower in children visited daily than in those visited weekly, suggesting a marked effect of frequent visits on estimated incidence rates. We conclude that the age pattern of malaria detected through ACD is a more robust epidemiological indicator than absolute incidence rate estimates and that, in contrast to the surrounding area, Ifakara town is subject to only moderate perennial malaria transmission.

Inter-observer variation in the assessment of clinical signs in sick Tanzanian children.

We assessed the inter-observer agreement in identification of a range of 24 clinical signs associated with disease presentation in 327 children aged < 5 years admitted to hospital in January-June 1999 in Ifakara, southern Tanzania. Children with diagnoses of malaria, pneumonia, diarrhoea, anaemia and malnutrition were examined independently by 2 clinical officers. Findings were recorded on a standard proforma. The Kappa-statistic was used to assess inter-observer agreement for each sign. Physical signs were more likely to be agreed upon by clinicians if they involved inspection than if they involved auscultation. The signs included in the Integrated Management of Childhood Illness (IMCI) algorithm were found to be largely appropriate (Kappa-scores > 0.41) although there was only fair agreement (Kappa-score 0.21-0.40) in the detection of neck stiffness and chest indrawing and slight agreement in the detection of dehydration (Kappa-score 0.199). All objective neurological signs were less reliably assessed in infants than in older children. The difficulties surrounding the diagnosis of impaired consciousness in young children should increase vigilance in the diagnosis and management of neurological complications of illnesses in infancy.

Effect of malaria on soluble transferrin receptor levels in Tanzanian infants.

The diagnosis of iron deficiency anemia in malaria endemic areas is complicated by the influence of the infection on the laboratory tests conventionally used to assess iron status. Determination of soluble transferrin receptor (sTfR) levels has been shown to be a sensitive indicator of iron deficiency in adults and is not affected by a range of infectious and inflammatory conditions. The utility of sTfR levels in the diagnosis of iron deficiency in malaria endemic areas remains unresolved. Three hundred and fourteen infants in a rural area of southern Tanzania living under conditions of intense and perennial malaria transmission were studied to determine the utility of sTfR plasma levels in the assessment of iron deficiency anemia. Independent of the presence of anemia, malaria parasitemia was associated with a significant increase in sTfR plasma levels that were even higher than those found in iron deficiency anemia. We conclude that the measurement of sTfR levels does not have a role in the diagnosis of iron deficiency anemia in young children exposed to malaria infection.

Intermittent treatment for malaria and anaemia control at time of routine vaccinations in Tanzanian infants: a randomised, placebo-controlled trial.

BACKGROUND: Clinical malaria and severe anaemia are major causes of paediatric hospital admission and death in many malaria-endemic settings. In the absence of an effective and affordable vaccine, control programmes continue to rely on case management while attempting the large-scale deployment of insecticide-treated nets. We did a randomised, placebo-controlled trial to assess the efficacy and safety of intermittent sulphadoxine-pyrimethamine treatment on the rate of malaria and severe anaemia in infants in a rural area of Tanzania. METHODS: We randomly assigned 701 children living in Ifakara, southern Tanzania, sulphadoxine-pyrimethamine or placebo at 2, 3, and 9 months of age. All children received iron supplementation between 2 and 6 months of age. The intervention was given alongside routine vaccinations delivered through WHO's Expanded Program on Immunisation (EPI). The primary outcome measures were first or only episode of clinical malaria, and severe anaemia in the period from recruitment to 1 year of age. Morbidity monitoring through a hospital-based passive case-detection system was complemented by cross-sectional surveys at 12 and 18 months of age. Results were expressed in terms of protective efficacy (100 [1-hazard ratio]%) and analysis was by intention to treat. FINDINGS: 40 children dropped out (16 died, 11 migrated, 12 parents withdrew consent, and one for other reasons). Intermittent sulphadoxine-pyrimethamine treatment was well tolerated and no drug-attributable adverse events were recorded. During the first year of life, the rate of clinical malaria (events per person-year at risk) was 0.15 in the sulphadoxine-pyrimethamine group versus 0.36 in the placebo group (protective efficacy 59% [95% CI 41-72]), and the rate of severe anaemia was 0.06 in the sulphadoxine-pyrimethamine group versus 0.11 in the placebo group (50% [8-73]). Serological responses to EPI vaccines were not affected by the intervention. INTERPRETATION: This new approach to malaria control reduced the rate of clinical malaria and severe anaemia by delivering an available and affordable drug through the existing EPI system. Data are urgently needed to assess the potential cost-effectiveness of intermittent treatment in areas with different patterns of malaria endemicity.

Prenatal risk factors of wheezing at the age of four years in Tanzania.

BACKGROUND: A study was undertaken to assess the interactions between prenatal exposures, early life infections, atopic predisposition, and allergen exposures in the development of wheezing up to the age of 4 years in a tropical region of Africa. METHODS: The study subjects comprised children born at the district hospital in Ifakara, Tanzania during a 1 year period who were participating in a trial of iron supplementation and malaria chemoprophylaxis during the first year of life and followed for up to 4 years. From this group of subjects, 658 (79%) participated in the interview at 18 months and 528 (64%) in a second interview at 4 years. Wheezing was measured with the ISAAC questionnaire. A hospital based inpatient and outpatient surveillance system was set up to document all attendance by study children for any cause, including episodes of clinical malaria and lower respiratory tract infections. Total IgE levels and malaria parasites were measured in maternal and cord blood. Total IgE was also measured at 18 months of age. Indoor environmental levels of Der p I and Fel d I were determined using an enzyme linked immunosorbent assay at the same time as the interview at the age of 18 months. RESULTS: The prevalence of wheezing at 4 years is common in Ifakara (14%, range 13-15%). The presence of malaria parasites in cord blood (odds ratio, OR = 6.84, 95% CI 1.84 to 24.0) and maternal asthma (OR = 8.47, 95% CI 2.72 to 26.2) were positively associated with wheezing at the age of 4 years, and cord blood total IgE was negatively associated (OR = 0.24, 95% CI 0.07 to 0.85) (all p<0.05). Parasitaemia at birth was not related to total IgE levels in cord blood (p=0.6). Clinical episodes of malaria during infancy were not associated with wheezing, and nor were levels of indoor aeroallergens. CONCLUSION: These findings suggest that events occurring during pregnancy may play a role in the future appearance of wheezing, although the results must be interpreted with caution because of the small numbers studied.

Placental malaria is associated with cell-mediated inflammatory responses with selective absence of natural killer cells.

Immunosuppression, particularly of cell-mediated responses, has classically been thought to play a major role in the increased susceptibility to malaria observed in pregnant women. An immunohistochemical characterization of the inflammatory infiltrate in a group of 41 placentas from women living in a Plasmodium falciparum-hyperendemic area in Tanzania revealed a marked increase in the number of monocytes and macrophages and cytotoxic T cells in the intervillous space of placentas with active malaria infection, compared with noninfected placentas, placentas from women with past infection, and a control group of placentas from Spain. This increase was associated with the severity of the infection. High numbers of monocytes and macrophages were associated with low birth weight. We also detected a complete absence of NK cells in the intervillous space in all placentas. This apparently physiological absence of NK cells may contribute to hindering the clearance of the parasite. These results indicate that placental malaria does not appear to be associated with cell-mediated immunosuppression. The role of the absence of NK cells in increased susceptibility to malaria needs to be further elucidated.

Diarrhea in children under 5 years of age from Ifakara, Tanzania: a case-control study.

A matched case-control study was conducted in the Maternal and Child Health Clinic (MCH) in Ifakara, Tanzania, during the rainy season in order to elucidate the risk factors for and etiology of diarrheal diseases in children under 5 years of age. Cases (103) and controls (206) were matched for sex and age group. Precoded questionnaires with demographic details, clinical history, and physical signs were completed. Stools samples were collected for bacterial, parasitological, and viral studies. A high number of siblings (odds ratio [OR], 0.86; P = 0.027), the number of siblings surviving (OR, 0.82; P = 0.007), the birth order (OR, 0.85; P = 0.018) and the distance from the house to the water source (OR, 0.33; P = 0.011) were associated with the risk of diarrhea. There were high rates of enteropathogen isolates in stool samples from children without diarrhea (52.23%). Shigella species were the only enteropathogen statistically related with diarrhea (OR, 2.90; P < 0.029). Enterotoxigenic, enteropathogenic, and enteroaggregative strains of Escherichia coli were not related with diarrhea, and neither were Giardia lamblia or Salmonella species.

Humoral immune responses during a malaria vaccine trial in Tanzanian infants.

The development of a malaria vaccine is a priority for improved and sustained malaria control. Optimal use of a vaccine in Africa will only be achieved if it can be delivered through the Expanded Programme of Immunization (EPI). We have completed a trial of the peptide vaccine SPf66 in Tanzanian infants, given alongside the EPI vaccines. This paper describes the humoral responses to SPf66 and the EPI vaccines. A total of 1207 infants were recruited into a two-arm, double-blind, individually randomized placebo-controlled trial of SPf66. The objectives of the trial were to determine the safety, immunogenicity and efficacy of SPf66 and to assess interactions with EPI vaccines when three doses of SPf66 were delivered alongside the EPI vaccines. Cross-sectional surveys were carried out to asses seroconversion rates to the EPI vaccines and the antibody response to SPf66 (NANP)50 and Plasmodium falciparum lysates. Seroconversion rates to EPI vaccines were high and no statistically significant differences in prevalence or titres were found between SPf66 and placebo recipients. IgG antibodies against SPf66 (NANP)50 and whole P. falciparum lysate were present in high titres in mothers of recruited children at the time of birth. Vaccination with SPf66 stimulated a good anti-SPf66 IgG response which declined to preimmunization levels by 2 years of age and which was not associated with protection against clinical malaria. The vaccine induced no IgG antibodies against (NANP)50 or P. falciparum lysates. SPf66 stimulated a humoral immune response when given to very young infants and did not interfere with seroconversion to EPI vaccines. The response to SPf66 was qualitatively different from that seen in older children, in whom SPf66 has been shown to be moderately efficacious. This difference raises concerns about the difficulties of immunizing very young infants who need to be targeted by antimalarial vaccination programs.

The association between atopy and asthma in a semirural area of Tanzania (East Africa).

BACKGROUND: Atopy is consistently associated with asthma, except in a study in Africa. We assessed the association between atopy and asthma in women from a semirural area of Tanzania (East Africa). METHODS: All pregnant women delivering at the district hospital during a 1-year period were recruited (n = 658, 60.6% of those selected). Asthma was investigated by a standard questionnaire and atopy by specific IgE (immunoglobulin E) antibodies to Dermatophagoides pteronyssinus (Der p 1) and cockroach. RESULTS: The prevalence of wheezing chest was 10.7%; of asthma, 3.5%. Levels of specific IgE of >0.35 kU/l (73%) and high levels of total IgE (62% higher than 1000 kU/l) were highly prevalent. Specific IgE antibody levels in sera were not associated with asthma (3.8% of women with negative specific IgE to any antigen had asthma in comparison to 4.0% of women with positive specific IgE; odds ratio [OR] = 1.06, 0.35-3.22). Total IgE was not different between women with asthma and women without asthma (P=0.36). CONCLUSIONS: In tropical regions, the association between allergy and asthma is complex, and specific IgE reactivity to environmental allergens may not be related to asthma.

The impact of placental malaria on gestational age and birth weight.

Maternal malaria is associated with reduced birth weight, which is thought to be effected through placental insufficiency, which leads to intrauterine growth retardation (IUGR). The impact of malaria on preterm delivery is unclear. The effects of placental malaria-related changes on birth weight and gestational age were studied in 1177 mothers (and their newborns) from Tanzania. Evidence of malaria infection was found in 75.5% of placental samples. Only massive mononuclear intervillous inflammatory infiltration (MMI) was associated with increased risk of low birth weight (odds ratio ¿OR, 4.0). Maternal parasitized red blood cells and perivillous fibrin deposition both were associated independently with increased risk of premature delivery (OR, 3.2; OR, 2.1, respectively). MMI is an important mechanism in the pathogenesis of IUGR in malaria-infected placentas. This study also shows that placental malaria causes prematurity even in high-transmission areas. The impact of maternal malaria on infant mortality may be greater than was thought previously.

Placental pathology in malaria: a histological, immunohistochemical, and quantitative study.

To characterize the histological changes in malarial placentas and their relationship with parity and maternal and cord parasitemias, we conducted a histological study on 1,179 placentas from Ifakara, Tanzania, an area with intense and perennial malaria transmission. Immunohistochemical and quantitative studies for CD45, fibrin, and villous area were performed in 60 cases. Four hundred fifteen placentas (35.2%) showed parasites (active infections); in 303 of them, parasites co-existed with pigment covered by fibrin (chronic infections), and in 112 only parasites were detected (acute infections). Four hundred seventy-five cases (40.3%) showed hemozoin deposition without parasites (past infections). Of women with parasitized placentas, 46.3% did not show parasites in the peripheral blood. Basal membrane thickening (P = .002), fibrinoid necrosis (P = .004), and prominence of syncytial knots (P = .031) were associated with active malarial infection. No quantitative differences for perivillous fibrin deposition or villous area were found. The most significant association with active malarial infection was intervillous infiltration by mononuclear inflammatory cells (P < .001). Chronic infections were associated with the most severe changes, particularly intervillous mononuclear inflammation (OR, 28.7; 95% CI = 16.0 to 51.5, P< .001). Past infections showed only minimal differences with noninfected placentas. Primiparas showed chronic infections more frequently than multiparas (52% v 15%, P < .001). They also showed significantly higher placental parasitemias and intervillous inflammatory infiltrate. In conclusion, placental histology is more sensitive than peripheral blood examination in detecting malarial infection during pregnancy. Most malarial infections recover during pregnancy, leaving few residual changes in the placenta. Intervillous inflammation is the most frequent finding associated with malaria and is especially severe in primiparas, suggesting that mechanisms other than immunosuppression are responsible for the high susceptibility in this group.

Cost-effectiveness of iron supplementation and malaria chemoprophylaxis in the prevention of anaemia and malaria among Tanzanian infants.

Prerequisites for effective interventions against severe anaemia and malaria among infants are economic evaluations to aid the setting of priorities and the making of health policy. In the present study we analysed the cost and effectiveness of three control strategies hypothetically delivered through the Expanded Programme on Immunization (EPI). For the prevention of severe anaemia and from the perspective of the health provider, the cost-effectiveness ratios were, respectively, US$ 8, US$ 9, and US$ 21 per disability-adjusted life year (DALY) for malaria chemoprophylaxis with Deltaprim (a combination of 3.125 mg pyrimethamine and 25 mg dapsone) + iron, Deltaprim alone, or iron supplementation alone. For malaria prevention, Deltaprim + iron cost US$ 9.7 per DALY and Deltaprim alone cost US$ 10.2 per DALY. From a sociocultural perspective the cost-effectiveness ratios ranged from US$ 9 to US$ 26 for severe anaemia prevention and from US$ 11 to US$ 12 for the prevention of clinical malaria. These ratios were highly cost-effective, as defined by the World Bank's proposed threshold of less than US$ 25 per DALY for comparative assessments. Furthermore, all the preventive interventions were less costly than the current malaria and anaemia control strategies that rely on clinical case management. This economic analysis supports the inclusion of both malaria chemoprophylaxis and iron supplementation delivered through EPI as part of the control strategies for these major killers of infants in parts of sub-Saharan Africa.

African children with malaria in an area of intense Plasmodium falciparum transmission: features on admission to the hospital and risk factors for death.

Malaria remains the most important parasitic cause of mortality in humans. Its presentation is thought to vary according to the intensity of Plasmodium falciparum transmission. However, detailed descriptions of presenting features and risk factors for death are only available from moderate transmission settings. Such descriptions help to improve case management and identify priority research areas. Standardized systematic procedures were used to collect clinical and laboratory data on 6,624 children admitted to hospital over a 1-year period in an intensely malarious part of Tanzania. Frequencies of signs and symptoms were calculated and their association with a fatal outcome was assessed using multivariate logistic regression. There were 72 deaths among 2,432 malaria cases (case fatality rate [CFR] = 3.0%); 44% of the cases and 54% of the deaths were in individuals less than 1 year of age. There was no association between level of parasitemia and CFR. Increased risk of dying was independently found in all children with hypoglycemia (odds ratio [OR] = 6.7, 95% confidence interval [CI] = 3.9-11.7), in children 1-7 months of age with tachypnea (OR = 8.8, 95% CI = 2.6-30.5) and dehydration (OR = 5.0, 95% CI = 1.9-14.2), and in children 8 months to 4 years of age with chest indrawing (OR = 4.7, 95% CI = 2.0-11.2) and inability to localize a painful stimulus (OR = 6.9, 95% CI = 2.9-16.5). Children in the bottom quartile of weight-for-age were more likely to die (OR = 2.1, 95% CI = 1.3-3.5). Eight percent of the malaria cases had severe anemia (packed cell volume < 15%) but 24% received a blood transfusion. The epidemiology of malaria disease may be more complex than previously thought. Improved case management in a wide variety of health facilities may result from adequate identification and treatment of dehydration and hypoglycemia. Transfusion-requiring anemia is a major problem and sustainable, effective preventive measures are urgently needed.

Prevalence and mother-to-infant transmission of hepatitis viruses B, C, and E in Southern Tanzania.

Hepatitis B and C markers were tested in 980 pregnant women, in the infants born to infected mothers, and in a random sample of 42 and 50, respectively, children born to uninfected mothers in Tanzania. Sixty-two women (6.3%) were positive for HBsAg and 15 (24%) were HBeAg-seropositive. Anti-HCV was detected in 49 women (5%), 15 (31%) of whom had detectable viremia. HCV RNA serum levels were low and only genotype 4 was identified. Sixty-six women (6.7%) were positive for anti-HIV, six of whom were coinfected with HBV and one with HCV. Anti-HEV was negative in the 180 women tested. At 8 months of age, HBsAg was detected in 8% and 2% of children born to HBV-infected and noninfected mothers, respectively (P = 0.2). Corresponding figures at 18 months of age were 31% and 21% (P = 0.3). When tested at 2 months of age, HCV RNA was not detected in any of the 43 children born to anti-HCV-positive mothers nor in any of 50 children born to anti-HCV-negative mothers. At 18 months, only one child, born to an anti-HCV-positive mother, had detectable HCV RNA. None of the infants born to women with HIV coinfection were infected with hepatitis viruses. This study suggests that exposure to HEV does not occur in southern Tanzania. The prevalence of current HBV infection in pregnant women from rural Tanzania is lower than in other sub-Saharan areas. In early childhood, HBV infection appears to occur by horizontal rather than maternofilial mechanisms of transmission. The prevalence of HCV infection is similar to that in other African countries. The results of this study show for the first time in Africa that mother-to-infant transmission does not play a significant role in the acquisition of HCV infection.

Evaluation of the SPf66 vaccine for malaria control when delivered through the EPI scheme in Tanzania.

BACKGROUND: Malaria control programmes need to protect young children, who bear the brunt of malaria disease and death in Africa. The development of a vaccine is a priority if improved and sustained malaria control is to be achieved. The best use of a vaccine in Africa will be achieved if it can be delivered through the expanded programme of immunization (EPI). We conducted a trial designed to evaluate the efficacy of SPf66 vaccine for malaria control when delivered through the EPI scheme in Tanzania. METHODS: The study was a two-arm, double blind, individually randomized placebo controlled trial involving 1207 infants. The primary objective of the trial was to estimate the efficacy of three doses of SPf66 given at 1, 2 and 7 months of age in preventing clinical episodes of malaria. These were documented through a health facility-based passive case detection system. RESULTS: Among 1207 randomized children, overall compliance for third dose was 91%. SPf66 was safe, immunogenic and did not interfere with the humoral immune responses to EPI vaccines. There were 294 children among SPf66 recipients and 288 among placebo recipients with at least one malaria episode, yielding a vaccine efficacy estimate of 2% (95% CI: -16, 16; P = 0.84). CONCLUSION: This has been the first trial of a malaria vaccine among very young infants. It provides information on the safety of peptide vaccines administered at this early age as well as their capacity to induce immune responses without negatively interacting with EPI vaccines. Given the modest protection previously documented in older age groups and the lack of efficacy in younger infants, this vaccine in its current alum-based formulation does not appear to have a role in malaria control in sub-Saharan Africa. The lack of efficacy found in this trial also raises concerns about potential difficulties of inducing protective immune responses against malaria through immunization in infants.

Safety in infants of SPf66, a synthetic malaria vaccine, delivered alongside the EPI.

The most likely mechanism to deliver a malaria vaccine in African countries is through the Expanded Program of Immunization (EPI). So far only SPf66, a multistage synthetic peptide, has shown any evidence of protection in Phase III field trials. In Tanzania, SPf66 reduced the risk of clinical malaria by 31% in children aged 1-5 years. In order to progress in the critical path of vaccine development and testing towards the implementation of a new vaccine in malaria control programs, we carried out a randomized double-blind placebo controlled efficacy trial of SPf66 when given alongside the EPI scheme. Monitoring of safety and reactogenicity during this trial included detailed clinical and laboratory assessments on 98 infants and assessment of adverse effects within 1 h of vaccination for all 1207 children vaccinated. Surveillance systems monitored attendances as outpatients, admissions to hospital and fatal events in the community. No serious adverse effects were detected more frequently amongst SPf66 recipients compared to placebo. This first assessment in very young infants of a synthetic vaccine provides evidence of a good safety profile.

Molecular evidence of mother-to-infant transmission of hepatitis G virus among women without known risk factors for parenteral infections.

Hepatitis G virus (HGV) RNA was detected in 18 of 133 pregnant women from Tanzania without known risk factors for HGV infection and in 7 of 18 children born to HGV RNA-positive mothers. Molecular evidence of mother-to-infant transmission was obtained only for three of seven children. HGV RNA was also detected in 4 of 42 children born to non-HGV-infected women. Thus, mechanisms other than materno-filial may play an important role in HGV transmission during early childhood.

Massive chronic intervillositis of the placenta associated with malaria infection.

Massive chronic intervillositis (MCI) is an infrequently recognized placental lesion thought to be of immunologic origin that has been associated with poor fetal outcome. It is characterized by a prominent inflammatory infiltrate in the intervillous space, composed mainly of monocytes and macrophages that can simulate a maternal malignant disorder involving the placenta. The villi are characteristically spared. We report 74 cases of placental malarial infection with morphologic features of MCI. In all cases, the massive inflammatory infiltrate was limited to the intervillous space, which appeared largely obliterated. Increased fibrin deposition and prominent syncytial knots were frequent associated findings. Inflammatory cells were CD45 and CD68 positive, consistent with a monocyte-macrophage population. Some polymorphonuclear leukocytes and scattered T and B lymphocytes were also present. Villi were not inflamed. Malarial pigment was present in all cases, and parasitized maternal erythrocytes were evident in 73 of 74 patients. The histologic pattern of MCI was observed in 17.6% of placentas with malarial parasites. Malarial MCI affected predominantly primigravida women (77%) and was associated with a reduced birth weight, which in 39 (53%) of the infants was less than 2500 g, and a low gestational age. None of the infants with placentas with MCI died in the early neonatal period. Morphologic changes of MCI are seen in a significant percentage of placentas with malarial infection, especially in primigravida women, and are associated with a low birth weight. Malarial infection should therefore be considered in the differential diagnosis of massive intervillous infiltrates.