Prevalence and risk of Plasmodium falciparum and P. vivax malaria among pregnant women living in the hypoendemic communities of the Peruvian Amazon

The Amazon region of Iquitos, Peru is hypoendemic for Plasmodium vivax and P. falciparum. There is limited information regarding the epidemiology of malaria during pregnancy in this region. Passive surveillance for clinical malaria among pregnant women was conducted in eight health posts in 2004 and 2005. Community-based active surveillance was conducted to determine the incidence of malarial infection among pregnant women in the community of Zungarococha in 2004 and 2005. Passive surveillance demonstrated that pregnant women had a prevalence of clinical malaria of 7.5% in 2004 and 6.6% in 2005 compared with 20.6% and 22.4% of the total population. Active surveillance showed that pregnant women were 2.3 (95% confidence interval = 1.32-3.95, P = 0.004) times more likely to have a P. falciparum infection compared with non-pregnant women. This study demonstrated that because of detection bias, passive surveillance underestimates the burden of malarial infection during pregnancy, and that subclinical malarial infections may occur frequently among pregnant women in this region. Furthermore, pregnant women in this low-transmission and P. vivax-dominant setting, experience an increased risk for P. falciparum infection, but not P. vivax infection.     

Demographic risk factors for severe and fatal vivax and falciparum malaria among hospital admissions in northeastern Indonesian Papua

Between January 1998 and December 2000, the Jayapura Provincial Public Hospital in northeastern Indonesian New Guinea (Papua) admitted 5,936 patients with a diagnosis of malaria. The microscopic diagnosis at admission was Plasmodium falciparum (3,976, 67%), Plasmodium vivax (1,135, 19%), Plasmodium malariae (8, < 1%), and mixed species infections (817, 14%). Approximately 9% (367) of patients were classified as having severe malaria (277 P. falciparum, 36 P. vivax, 53 mixed infections, and 1 P. malariae) and 88 died (79 P. falciparum/mixed infections and 9 P. vivax). Risk of fatal outcomes among severe malaria patients was indistinguishable between those with falciparum versus vivax malaria (OR = 0.89; P = 0.771). Compared with non-pregnant women, pregnant women showed no higher risk of severe malaria (P = 0.643) or death caused by severe malaria (P = 0.748). This study compares admissions per population (based on census data), parasitemia, morbidity, and mortality among children versus adults, pregnant versus non-pregnant women, and urban/suburban versus rural residents.     

Reduced prevalence of Plasmodium falciparum infection and of concomitant anaemia in pregnant women with heterozygous G6PD deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency confers protection against malaria in children, yet its role in malaria in pregnancy is unknown. In a cross-sectional study among 529 pregnant Ghanaian women, Plasmodium falciparum infection, anaemia and G6PD genotypes were assessed. Of these, 30.4% were heterozygous and 2.6% were homozygous for G6PD deficiency. The prevalence of P. falciparum infection decreased from 66% in G6PD-normal women to 58% in heterozygotes, and to 50% in individuals with homozygous G6PD deficiency (Chi2(trend) = 4.4, P = 0.04). Multivariate analysis revealed that in multigravid women but not in primigravidae, heterozygous G6PD deficiency was associated with a reduced risk of P. falciparum infection (Odds ratio (OR), 0.6; 95% confidence interval (95% CI), [0.4-0.9]). This protection against infection was limited to the third trimenon of pregnancy. In addition, heterozygous G6PD deficiency was associated with a reduced risk of anaemia among infected multigravidae (OR, 0.5 [0.3-1.0]). Pregnancy is a period of high vulnerability to malaria. The results of this study provide evidence for protection against malaria in pregnancy caused by heterozygous G6PD deficiency. This advantage, even if confined to multigravid women, may contribute to the selection of G6PD variants in malaria-endemic regions.     

Specific stimulation of HIV-1 replication in human placental trophoblasts by an antigen of Plasmodium falciparum

Epidemiological data point to an increased risk of HIV-1 mother-to-child transmission in pregnant women with malaria, by unknown mechanisms. We show here that surface binding of a recombinant Plasmodium falciparum adhesin to chondroitin sulphate A proteoglycans increases HIV-1 replication in the human placental cell line BeWo, probably by a P. falciparum adhesin-induced long-terminal repeat-driven TNF-alpha stimulation. This suggests that placental malaria could increase the risk of HIV-1 transmission in utero.     

Prevalence of asymptomatic malaria parasitaemia amongst pregnant women

Two hundred and forty-six apparently healthy pregnant women aged 19-40 years, without symptoms were recruited (147 recruited during the dry season and 99 recruited during the rainy season) for the present study. Blood examinations for malaria parasites, Plasmodium falciparum specific-IgG concentration and serological reactivity with P. falciparum-histidine rich protein-2 (HRP-2) antigens were conducted on all the pregnant women during the dry and rainy seasons of the year. During the dry season, 109 (74%) of the recruited pregnant women without symptoms had P. falciparum parasitaemia, while 79 (80%) of the recruited pregnant women without symptoms had P. falciparum parasitaemia during the rainy season. However, the P. falciparum malaria parasites density was significantly raised during the dry season compared with that of in the rainy season (p < 0.05). Serological analysis with P. falciparum histidine rich protein-2 antigen (HRP-2) showed 108 (73%) and 71 (77%) of the pregnant women without symptoms as seropositive during the dry and rainy seasons respectively. The P. falciparum specific-IgG concentration was similar during both seasons in the HRP-2 seropositive pregnant women without symptoms (p > 0.05). The results showed no seasonal tide in the incidences of asymptomatic P. falciparum parasitaemia; however, the significantly raised parasitaemia during the dry season may suggest possible increased parasites tolerance. The P. falciparum specific-IgG concentration during both seasons may not be the primary effector mechanism offering tolerance in asymptomatic parasitaemia in pregnant women.     

Epidemiology and burden of malaria in pregnancy

We reviewed evidence of the clinical implications and burden of malaria in pregnancy. Most studies come from sub-Saharan Africa, where approximately 25 million pregnant women are at risk of Plasmodium falciparum infection every year, and one in four women have evidence of placental infection at the time of delivery. P falciparum infections during pregnancy in Africa rarely result in fever and therefore remain undetected and untreated. Meta-analyses of intervention trials suggest that successful prevention of these infections reduces the risk of severe maternal anaemia by 38%, low birthweight by 43%, and perinatal mortality by 27% among paucigravidae. Low birthweight associated with malaria in pregnancy is estimated to result in 100,000 infant deaths in Africa each year. Although paucigravidae are most affected by malaria, the consequences for infants born to multigravid women in Africa may be greater than previously appreciated. This is because HIV increases the risk of malaria and its adverse effects, particularly in multigravidae, and recent observational studies show that placental infection almost doubles the risk of malaria infection and morbidity in infants born to multigravidae. Outside Africa, malaria infection rates in pregnant women are much lower but are more likely to cause severe disease, preterm births, and fetal loss. Plasmodium vivax is common in Asia and the Americas and, unlike P falciparum, does not cytoadhere in the placenta, yet, is associated with maternal anaemia and low birthweight. The effect of infection in the first trimester, and the longer term effects of malaria beyond infancy, are largely unknown and may be substantial. Better estimates are also needed of the effects of malaria in pregnancy outside Africa, and on maternal morbidity and mortality in Africa. Global risk maps will allow better estimation of potential impact of successful control of malaria in pregnancy.     

Malaria during pregnancy and infancy, in an area of intense malaria transmission in central India

The clinico-epidemiological pattern of malarial infection in a cohort of pregnant women and infants was analysed during a malaria epidemic (1997-1998). The subjects were all members of tribal communities in an isolated and almost inaccessible area of central India. Overall, 151 (55%) of the 274 pregnant women investigated were found to have malarial infections at some time during the study, with Plasmodium falciparum predominating (88% of infections). All of the women investigated, whether primigravidae (42% found infected), secundigravidae (68%) or multigravidae (54%), were at great risk of developing severe malaria. When trimesters were compared, the highest prevalence of P. falciparum infection was recorded in the second (59% infected), irrespective of parity. Of the women found infected with P. falciparum, 3% had abortions, 4% stillbirths and 2% had babies who died while neonates. The small number of P. vivax infections observed prevented similar analyses for this species of parasite. Malarial infection was also seen in 218 (41%) of the 535 infants investigated. The values of age-specific prevalences revealed that > 30% of the infants examined at 2 months of age were then found to have P. vivax and/or P. falciparum parasitaemias. At 1 year of age, overall malaria prevalence was 50%, with P. vivax representing 25% of the infections and P. falciparum the rest. Subsequent follow-up revealed that three of the infants investigated, each of whom had had P. falciparum infections previously, died before their first birthdays. Re-infections (or treatment failures) were found to be common, both in the infants and the pregnant women. Pregnant women and infants from the study area clearly require systematic intervention to reduce their malaria-attributable morbidity.     

Malaria and the pregnant traveller

Malaria in pregnancy contributes to significant maternal and foetal mortality and morbidity in women in the tropics. Adverse effects for non-immune travellers are potentially devastating for mother and foetus. Women travellers should always be strongly advised against visiting malarious areas if they are pregnant or intend to get pregnant. Chemoprophylactic and treatment options for pregnant women (or those planning to conceive) are extremely limited and lag behind what can currently be offered to non-pregnant travellers. This is because of spread of multi-resistant strains of P. falciparum. Personal protection from malaria vectors remains essential. Mosquito-net and skin repellents (DEET (20%)) are effective. Diagnosis of malaria in travellers is difficult and is more likely to be missed in pregnant travellers due to lower parasitaemia. Pregnant women can succumb rapidly to severe malaria. Should the returned traveller survive an episode of malaria in pregnancy and go on to deliver, the adverse effects on the infant are potentially irreversible. These risks need to be clearly communicated.     

A randomized comparison of artesunate-atovaquone-proguanil versus quinine in treatment for uncomplicated falciparum malaria during pregnancy

BACKGROUND: There is no safe, practical, and effective treatment for pregnant women infected with multidrug-resistant Plasmodium falciparum. METHODS: We recruited pregnant Karen women in the second or third trimesters of pregnancy who had uncomplicated falciparum malaria for a randomized, open-label trial with a restricted sequential trial design of 7 days of supervised quinine (SQ7) versus 3 days of artesunate-atovaquone-proguanil (AAP). RESULTS: Eight-one pregnant women entered the study between December 2001 and July 2003; 42 were treated with SQ7 and 39 were treated with AAP. Fever, parasite clearance, and duration of anemia were significantly better with AAP; the treatment failure rate was 7 times lower (5% [2/39] vs. 37% [15/41]; relative risk, 7.1 [95% confidence interval, 1.7-29.2]; P = .001). There were no significant differences in birth weight, duration of gestation, or congenital abnormality rates in newborns or in growth and developmental parameters of infants monitored for 1 year. CONCLUSION: AAP is a well-tolerated, effective, practical, but expensive treatment for multidrug-resistant falciparum malaria during the second or third trimesters of pregnancy. Despite the small number of subjects, our results add to the growing body of evidence that AAP is safe for the mother and the fetus.     

Human immunodeficiency virus seropositivity and malaria as risk factors for third-trimester anemia in asymptomatic pregnant women in western Kenya.

To assess risk factors for anemia in late pregnancy, we studied healthy pregnant women with a singleton uncomplicated pregnancy of > or = 32 weeks attending the prenatal clinic in the Provincial Hospital in Kisumu, Kenya. Between June 1996 and December 1998, 4,608 pregnant women had a blood sample collected for hemoglobin (Hb) measurement, malaria smear, and testing for human immunodeficiency virus (HIV). The mean +/- standard deviation of Hb was 9.58 +/- 1.8 g/dL; 21% had malaria in their blood; and 25% of the women were HIV seropositive. Plasmodium falciparum parasitemia was more common among HIV-seropositive women in all gravidities compared with HIV-seronegative women (risk ratio, 1.71; 95% confidence interval, 1.53-1.92). In a multivariate analysis, for primi- and secundigravidae women, the factors malaria, belonging to the Luo tribe, and HIV seropositivity were significantly associated with any anemia (Hb < 11 g/dL), and HIV seropositivity and documented fever were associated with severe anemia (Hb < 7 g/dL). In women of higher gravidities, HIV seropositivity was the only statistically significant factor associated with any anemia or with severe anemia. Asymptomatic HIV seropositivity is an important risk factor to be considered in the differential diagnosis of maternal anemia, independent of P. falciparum parasitemia.     

Circulating receptors implicated in the cyto-adherence occurring in severe Plasmodium falciparum malaria in Thailand

The kinetic profiles of soluble chondroitin-sulphate A (CSA), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin were investigated in 17 patients hospitalized with Plasmodium falciparum malaria. The aim was to see if these circulating adhesion molecules could be considered as markers for the severity of P. falciparum malaria. The levels of all the adhesion molecules were found to be higher in the sera from all the malaria cases, both severe and uncomplicated, than in those from uninfected controls. The elevation in plasma CSA, reported for the first time, was statistically very significant (P = 0.00001). However, when severe cases were compared with the uncomplicated, there were no significant differences in the level of any of the receptors except ICAM-1, which was highest in those with the severe disease (P = 0.01). The absence of any significant correlation between the plasma concentration of CSA and malaria severity indicates that this adhesion molecule could not be used to predict the severity of malaria, although its role in sequestration of the parasites in pregnant women is well established.     

The risk of malarial infections and disease in Papua New Guinean children

In a treatment re-infection study of 206 Papua New Guinean school children, we examined risk of reinfection and symptomatic malaria caused by different Plasmodium species. Although children acquired a similar number of polymerase chain reaction-detectable Plasmodium falciparum and P. vivax infections in six months of active follow-up (P. falciparum = 5.00, P. vivax = 5.28), they were 21 times more likely to develop symptomatic P. falciparum malaria (1.17/year) than P. vivax malaria (0.06/year). Children greater than nine years of age had a reduced risk of acquiring P. vivax infections of low-to-moderate (>150/microL) density (adjusted hazard rate [AHR] = 0.65 and 0.42), whereas similar reductions in risk with age of P. falciparum infection was only seen for parasitemias > 5,000/microL (AHR = 0.49) and symptomatic episodes (AHR = 0.51). Infection and symptomatic episodes with P. malariae and P. ovale were rare. By nine years of age, children have thus acquired almost complete clinical immunity to P. vivax characterized by a very tight control of parasite density, whereas the acquisition of immunity to symptomatic P. falciparum malaria remained incomplete. These observations suggest that different mechanisms of immunity may be important for protection from these malaria species.     

Microscopic and sub-microscopic Plasmodium falciparum infection, but not inflammation caused by infection, is associated with low birth weight

Pregnancy-associated malaria is one of the leading causes of low birth weight in malaria endemic areas. In this study, 145 parturient women residing in areas endemic for Plasmodium falciparum in Lambaréné, Gabon, were recruited into the study after delivery, and the association of maternal P. falciparum infection, inflammatory response, and birth weight was studied. At delivery, 10% (15) of the mothers (12 were positive in both peripheral and placental blood smears, 1 was positive in peripheral blood only, and 2 were positive in placenta blood only) were positive for P. falciparum by microscopy and 23% (30) by real-time polymerase chain reaction (PCR). The level of C-reactive protein (CRP) was significantly elevated in microscopically P. falciparum-positive pregnant women (34 mg/L; 95% CI: 3-458) but not in those with sub-microscopic infections (6 mg/L; 95% CI: 1-40) compared with those free of P. falciparum infection (7 mg/L; 95% CI: 1-43). In a multivariate analysis, the presence of microscopic (adjusted OR = 28.6, 95% CI = 4.8-169.0) or sub-microscopic (adjusted OR = 13.2, 95% CI = 2.4-73.0) P. falciparum infection in pregnant women and age of mothers < 21 years (adjusted OR = 9.7 CI = 1.0-89.7), but not CRP levels, were independent predictors for low birth weight. This finding may have important operational implications and emphasizes the need for appropriate diagnostic methods in studies evaluating the outcome of pregnancy-associated malaria.     

The immuno-epidemiology of pregnancy-associated Plasmodium falciparum malaria: a variant surface antigen-specific perspective

Women living in areas of intense P. falciparum transmission have acquired substantial protective immunity to malaria when they reach childbearing age. Nevertheless, pregnancies in such areas are associated with substantial malaria-related morbidity and mortality, particularly among women of low parity. The parity-dependency of susceptibility to malaria in pregnant women suggests that protective immunity to this type of malaria can be developed. However, until recently it has been poorly understood why the clinical protection against malaria, which young women in endemic areas acquire well before their first pregnancy, is suddenly rendered inadequate when they become pregnant, only to be regained during the course of a few pregnancies. In this article, I discuss some recent immuno-epidemiological studies of pregnancy-associated malaria, which, in combination with the generally improved understanding of how protective immunity to P. falciparum malaria operates and is acquired, have provided important insights into this enigma.     

Minimal association of common red blood cell polymorphisms with Plasmodium falciparum infection and uncomplicated malaria in Papua New Guinean school children

Southeast Asian ovalocytosis (SAO), α(+)-thalassemia, and low expression of complement receptor 1 (CR1) have been associated with protection against severe Plasmodium falciparum malaria. In a cohort of children 5-14 years of age the effect of α(+)-thalassemia, SAO (SLC4A1Δ27), CR1 polymorphisms, and Gerbich negativity (GYPCΔex3) on risk of P. falciparum infections and uncomplicated illness were evaluated. The risk of acquiring polymerase chain reaction (PCR)-diagnosed P. falciparum infections was significantly lower for α(+)-thalassemia heterozygotes (hazard ratio [HR]: 0.56) and homozygotes (HR: 0.51) than wild-type children. No such differences were seen in light of microscopy diagnosed infections (P = 0.71) or were α(+)-thalassemia genotypes associated with a reduced risk of uncomplicated P. falciparum malaria. No significant associations between the risk of P. falciparum infection or illness were observed for any of the other red blood cell polymorphisms (P > 0.2). This suggests that these polymorphisms are not associated with significant protection against P. falciparum blood-stage infection or uncomplicated malaria in school-aged children.     

Differential regulation of IgG subclasses and IgE antimalarial antibody responses in complicated and uncomplicated Plasmodium falciparum malaria

The aim of this study was to assess the immunoglobulin (Ig)-subclass distribution of antimalarial antibody responses in 110 and 169 Thai patients with complicated and uncomplicated Plasmodium falciparum malaria, respectively. Antimalarial plasma IgG subclasses and IgE antibody levels against a crude malaria blood stages, and antigen preparation were determined using enzyme-linked immunosorbent assay (ELISA). On admission, the levels of anti-P. falciparum IgG1, IgG2 and IgG3 were significantly lower in patients with complicated malaria than uncomplicated malaria (IgG1, P < 0.0001; IgG2, P < 0.0001; IgG3, P < 0.0001). The levels of antimalarial IgE were slightly lower, but not statistically significant (P = 0.389) in the complicated malaria. After adjusting all antibody levels and age, anti-P. falciparum IgG3 levels remained significantly associated with complicated malaria. None of the other antibody concentrations showed statistically significant associations with complicated malaria. The anti-P. falciparum IgG3 levels were related to the IgG1 as well as IgG2 levels. A correlation between anti-P. falciparum IgG2 and IgE was observed in the complicated malaria group, and this may indicate their roles in the severity of disease. Our data suggest that anti-P. falciparum IgG3 is associated with a reduced risk of complicated malaria and that antimalarial Ig-subclasses are differently regulated in patients with complicated and uncomplicated malaria.     

Falciparum malaria and pregnancy.

Falciparum malaria in pregnancy is a significant health problem in India. Pregnant women constitute an important high risk group for malaria infection which may cause abortion, still births, intra uterine growth retardation (IUGR), and pre-mature labour. Two hundred eighty-eight admitted female patients of falciparum malaria were included in the study out of which 45 were pregnant. The mortality rate was highly significant in pregnant females (37.77%) in comparison to non-pregnant females (14.81%); (p < 0.001). The incidence of various pernicious syndromes including cerebral malaria, severe anaemia (Hb < 5 g%) hepatic and renal failure were more in pregnant females in comparison to non-pregnant females. The incidence of infection was higher among primigravida and second gravida 30/45 (66.66%) as compared to multigravida 15/45 (33.33%) and the greater incidence of infection was seen during 14-28 wk of gestation 23/45 (51.11%). Pregnancy related complications in the form of preterm live birth (20%). Intra uterine death (IUD 31.11%), still births (13.33%) and abortions (11.11%) were more pronounced in primiparous women as compared to multiparous. Weight of placenta in majority of patients ranged between 200-400 g (22/31; 70.96%). Normal pregnancy continued in only 11 out of 45 pregnant females, out of which seven had low birth weight body (63.63%). As the pregnancy is associated with increased incidence and adverse outcome of falciparum malaria infection, chemoprophylaxis should be made an integral part of antenatal care along with antianaemic therapy to reduce the risk of serious maternal and fetal complications.     

Detection of Plasmodium falciparum in pregnancy by laser desorption mass spectrometry

Detection of Plasmodium falciparum malaria during pregnancy is complicated by sequestration of parasites in the placenta, which reduces peripheral blood microscopic detection. Laser desorption mass spectrometry (LDMS) has previously demonstrated sensitive detection of hemozoin from P. falciparum blood cultures and the ability to track parasitemia in a Plasmodium yoelii malaria mouse model. Here we use a simple, dilution in water, blood sample preparation protocol for LDMS detection of malaria in 45 asymptomatic, pregnant Zambian women. We compare LDMS to microscopy and polymerase chain reaction (PCR) analysis. All women were microscopy negative. LDMS detected P. falciparum hemozoin in 15 out of 45 women, while PCR results were positive in 25 women. Compared with PCR, which analyzed 20-30 microL of blood, the sensitivity of LDMS, which analyzed < 1 microL of blood, was 52%, with a specificity of 92%. LDMS is a potentially rapid and more sensitive alternate diagnostic method than microscopy.     

Prevalence of malaria as co-infection in HIV-infected individuals in a malaria endemic area of southeastern Nigeria

BACKGROUND & OBJECTIVE: The present study was conducted on the prevalence of malaria as co-infection amongst 'asymptomatic HIV' and 'symptomatic HIV' subjects to see if such prevalence deviated from that commonly reported in apparently health individuals in same locality. METHODS: A prospective study that involved 196 participants grouped according to their HIV status as: 'asymptomatic HIV seropositive group' (n = 101); 'symptomatic HIV seropositive group' (n = 48) and 'control HIV-seronegative group (n = 47). Blood samples collected from the participants were used for double HIV screening by rapid immunoassay technique and immunochromatographic technique, and for the diagnosis of Plasmodium falciparum malaria using rapid P. falciparum antigen detection method. RESULTS: The result showed that the prevalence of P. falciparum malaria as a co-infection amongst the asymptomatic HIV seropositive group was 12 (11.8%) and amongst the symptomatic HIV seropositive group was 16 (33.3%). However, the prevalence rate of P. falciparum malaria amongst the control HIV seronegative group was 5 (10.6%) and the combined burden of P. falciparum malaria amongst both groups of HIV seropositives was 28 (18.9%). INTERPRETATION & CONCLUSION: The present study observed different prevalence rates of P. falciparum malaria amongst the three groups. The prevalence was tripled in symptomatic HIV seropositive group. This shows a clear departure from possible obtainable prevalence of malaria infection alone in this malaria endemic area. Due to the mortality rates associated with malaria infection in an endemic area, it may be necessary that routine malaria screening be adopted as part of the management policy to check the co-infection.