Malaria congénita por Plasmodium falciparum / Congenital malaria by Plasmodium falciparum

INTRODUCCIÓN: La malaria congénita (MC) es la infección por Plasmodium spp adquirida in útero o durante el parto y sus manifestaciones clínicas son inespecíficas. Puede causar enfermedad grave en la embaraza da y en el recién nacido. OBJETIVO: describir dos casos de MC causados por Plasmodium falciparum, diagnóstico diferencial de sepsis en recién nacidos de gestantes que hayan visitado o residan en áreas endémicas para malaria. CASOS CLÍNICOS: Neonatos de sexo femenino, nacidos en área no endémica para malaria, diagnosticados con sepsis neonatal y tratados con antibióticos sin respuesta clínica. Después de la primera semana de vida la gota gruesa identificó trofozoítos de Plasmodium falciparum y los neonatos recibieron tratamiento con quinina intravenosa con mejoría. Las madres de las recién nacidas tuvieron malaria en el embarazo, una de ellas recibió tratamiento y estaba asintomática y otra tenía malaria complicada al momento del parto. CONCLUSIONES: La MC puede causar enfermedad neonatal grave con manifestaciones clínicas inespecíficas y similares a la sepsis, el tratamiento oportuno disminuye el riesgo de malaria complicada. Es un diagnóstico diferencial en recién nacidos de mujeres con malaria durante el embarazo o gestantes que visiten o residan en áreas endémicas.

INTRODUCTION: Congenital malaria (CM) is a Plasmodium spp infection acquired in utero or during delivery with nonspecific clinical manifestations. Plasmodium falciparum can cause severe illness in pregnant wo men and newborns. OBJECTIVE: to describe two cases of CM caused by Plasmodium falciparum, di fferential diagnosis of sepsis in newborns of pregnant women who live in or have visited endemic malaria zones. CLINICAL CASES: Female neonates born in a non-endemic malaria area, diagnosed with neonatal sepsis and treated with antibiotics without clinical response. After the first week of life, the peripheral blood smear identified trophozoites of Plasmodium falciparum thus the newborns were treated with intravenous quinine, improving their condition. The mothers of the two newborns who had malaria in pregnancy, one of them received treatment and she was asymptomatic, and the other one had severe malaria at the time of delivery. CONCLUSIONS: CM can cause severe neonatal disease with non-specific, sepsis-like clinical manifestations in which early treatment decreases the risk of complicated malaria. It is a differential diagnosis in newborns of women with a history of malaria during pregnancy or pregnant women visiting or living in endemic malaria areas.

What about the treatment of asymptomatic forms of congenital malaria: case report and review of the literature.

We report in this manuscript a case of newborn baby with asymptomatic form of congenital malaria; the screening of the peripheral blood smear of the baby after a positive result in the mother allowed the diagnosis. The authors were permitted through this case to discuss the therapeutic possibility in these cases.

Congenital malaria by Plasmodium falciparum. / Malaria congénita por Plasmodium falciparum.

Introdution: Congenital malaria (CM) is a Plasmodium spp infection acquired in utero or during delivery with nonspecific clinical manifestations. Plasmodium falciparum can cause severe illness in pregnant wo men and newborns. OBJECTIVE: to describe two cases of CM caused by Plasmodium falciparum, di fferential diagnosis of sepsis in newborns of pregnant women who live in or have visited endemic malaria zones. CLINICAL CASES: Female neonates born in a non-endemic malaria area, diagnosed with neonatal sepsis and treated with antibiotics without clinical response. After the first week of life, the peripheral blood smear identified trophozoites of Plasmodium falciparum thus the newborns were treated with intravenous quinine, improving their condition. The mothers of the two newborns who had malaria in pregnancy, one of them received treatment and she was asymptomatic, and the other one had severe malaria at the time of delivery. CONCLUSIONS: CM can cause severe neonatal disease with non-specific, sepsis-like clinical manifestations in which early treatment decreases the risk of complicated malaria. It is a differential diagnosis in newborns of women with a history of malaria during pregnancy or pregnant women visiting or living in endemic malaria areas.

Prevalence of congenital malaria in newborns of mothers co-infected with HIV and malaria in Benin city.

BACKGROUND: HIV and Plasmodium falciparum malaria co-infection annually complicates about one million pregnancies in sub-Saharan Africa. Congenital malaria (CM) has deleterious effects on newborns. Little is known about the effect of co-infections on the prevalence of CM in infants born by these women. This study was carried out to determine the prevalence of CM in newborns of mothers co-infected with HIV and malaria compared to HIV-negative mothers with malaria in Benin-City. METHODS: Subjects were 162 newborns of mothers co-infected with HIV and malaria. Controls were 162 newborns of HIV negative malaria infected mothers. Blood film for malaria parasites was done on cord blood and peripheral blood on days 1, 3 and 7 in the newborns. Maternal peripheral blood film for malaria parasite was done at delivery and placental tissue was obtained for confirmation of placental malaria by histology. Diagnosis of malaria in blood films was by light microscopy. RESULTS: The prevalence of CM in subjects was significantly higher than in controls (34.6% and 22.2%, p=.014). Profound immunodepression (maternal CD4 cell count <200 cell/mm3) was significantly associated with CM (p=.006). The major predictors of CM in subjects were maternal CD4 cell count <200 cell/mm3 and placental malaria while in controls placental malaria was the only predictor. CONCLUSIONS: Babies born to mothers co-infected with HIV and malaria are at increased risk for CM. All babies born by HIV positive mothers should be screened for CM.

Congenital Plasmodium falciparum Malaria in Washington, DC.

Congenital malaria is rare in the United States, but is an important diagnosis to consider when evaluating febrile infants. Herein, we describe a case of congenital Plasmodium falciparum malaria in a 2-week-old infant born in the United States to a mother who had emigrated from Nigeria 3 months before delivery.

Prevalence of gestational, placental and congenital malaria in north-west Colombia.

BACKGROUND: The frequency of pregnancy-associated malaria is increasingly being documented in American countries. In Colombia, with higher frequency of Plasmodium vivax over Plasmodium falciparum infection, recent reports confirmed gestational malaria as a serious public health problem. Thick smear examination is the gold standard to diagnose malaria in endemic settings, but in recent years, molecular diagnostic methods have contributed to elucidate the dimension of the problem of gestational malaria. The study was aimed at exploring the prevalence of gestational, placental and congenital malaria in women who delivered at the local hospitals of north-west Colombia, between June 2008 and April 2011. METHODS: A group of 129 parturient women was selected to explore the prevalence of gestational, placental and congenital malaria in a descriptive, prospective and transversal (prevalence) design. Diagnosis was based on the simultaneous application of two independent diagnostic tests: microscopy of thick blood smears and a polymerase chain reaction assay (PCR). RESULTS: The prevalence of gestational malaria (thick smear /PCR) was 9.1%/14.0%; placental malaria was 3.3%/16.5% and congenital malaria was absent. A history of gestational malaria during the current pregnancy was significantly associated with gestational malaria at delivery. Plasmodium vivax caused 65% of cases of gestational malaria, whereas P. falciparum caused most cases of placental malaria. CONCLUSIONS: Gestational and placental malaria are a serious problem in the region, but the risk of congenital malaria is low. A history of malaria during pregnancy may be a practical indicator of infection at delivery.

Plasmodium falciparum infection among neonates in the North Central region of Nigeria.

INTRODUCTION: This cross-sectional study investigated the rate of congenital and neonatal malaria infections in patients attending our hospital. METHODOLOGY: Thick and thin blood films of 288 neonates admitted in the Special Care Baby Unit of Jos University Teaching Hospital, Nigeria, were examined microscopically for malaria parasites. Babies' and mothers' demographic and clinical data were analyzed. RESULTS: Of 288 blood samples examined, 160 (55.6%) were from males, 115 (39.9%) were from babies 0 to 7 days old, and 173 (60.1%) were from babies 8 to 28 days old. In total, 91 (31.6%) babies had malaria parasitaemia, of whom 49 (53.8%) were males. Malaria was significantly higher in babies 8 to 28 days old (p < 0.001) and was independent of gender (p=0.692). Prevalence rates for congenital and neonatal malaria were 6.9% and 24.7% respectively. Clinical presentations on admission included fever, cough, pallor, jaundice, and inability to suck. A total of 145 (50.3%) babies had symptoms of malaria, of whom 56 (61.5%) had malaria parasitaemia. Symptoms of malaria were present in 35 (12.2%) babies of 59 (20.5%) mothers who had symptoms of malaria during pregnancy. Ten (11.0%) of these neonates had malaria parasitaemia, of whom 4 (0.4%) were 0 to -7 days old. Plasmodium falciparum was the only specie identified. No mortality was recorded against malaria-infected babies. CONCLUSION: High prevalence of malaria in these neonates calls for high index of suspicion. Inclusion of malaria parasite test in the routine battery of tests for babies presenting with clinical signs and symptoms of neonatal infections is recommended.

Prevalence of congenital malaria in high-risk Ghanaian newborns: a cross-sectional study.

BACKGROUND: Congenital malaria is defined as malaria parasitaemia in the first week of life. The reported prevalence of congenital malaria in sub-Saharan Africa is variable (0 - 46%). Even though the clinical significance of congenital malaria parasitaemia is uncertain, anti-malarial drugs are empirically prescribed for sick newborns by frontline health care workers. Data on prevalence of congenital malaria in high-risk newborns will inform appropriate drug use and timely referral of sick newborns. METHODS: Blood samples of untreated newborns less than 1 week of age at the time of referral to Korle Bu Teaching hospital in Accra, Ghana during the peak malaria seasons (April to July) of 2008 and 2010 were examined for malaria parasites by, i) Giemsa-stained thick and thin blood smears for parasite count and species identification, ii) histidine-rich protein- and lactic dehydrogenase-based rapid diagnosis tests, or iii) polymerase chain reaction amplification of the merozoite surface protein 2 gene, for identification of sub-microscopic parasitaemia. Other investigations were also done as clinically indicated. RESULTS: In 2008, nine cases of Plasmodium falciparum parasitaemia were diagnosed by microscopy in 405 (2.2%) newborns. All the nine newborns had low parasite densities (≤ 50 per microlitre). In 2010, there was no case of parasitaemia by either microscopy or rapid diagnosis tests in 522 newborns; however, 56/467 (12%) cases of P. falciparum were detected by polymerase chain reaction. CONCLUSION: Congenital malaria is an uncommon cause of clinical illness in high-risk untreated newborns referred to a tertiary hospital in the first week of life. Empirical anti-malarial drug treatment for sick newborns without laboratory confirmation of parasitaemia is imprudent. Early referral of sick newborns to hospitals with resources and skills for appropriate care is recommended.

Highly effective therapy for maternal malaria associated with a lower risk of vertical transmission.

BACKGROUND: The epidemiology of congenital malaria was investigated in a hospital-based malaria surveillance study in Papua, Indonesia. METHODS: From April 2005 to January 2010, 4878 delivering women and their newborns underwent prospective clinical review and malaria screening by peripheral blood microscopy. FINDINGS: Congenital malaria occurred in 8 per 1000 (38/4884) live births, with Plasmodium falciparum accounting for 76.3% (29) and P. vivax for 15.8% (6) of infections. Maternal malaria at delivery (adjusted odds ratio [AOR], 9.5; 95% confidence interval [CI], 4.2-21.5; P < .001), age ≤ 16 years (AOR, 4; 95% CI, 1.4-12.1; P = .011), and prior malaria during pregnancy (AOR, 2.2; 95% CI, 1.1-4.4, P = .022) were independent risk factors for vertical transmission. Of 29 mothers and neonates with contemporaneous peripheral parasitemia, 17% (5) had discordant parasite species, suggesting possible antenatal malaria transmission. Newborns with malaria were at significantly greater risk of low birth weight (AOR, 2.8; 95% CI, 1.2-6.6; P = .002). Following introduction of dihydroartemisinin-piperaquine for uncomplicated malaria in the second and third trimesters of pregnancy, congenital malaria incidence fell from 3.2% to 0.2% (odds ratio, 0.07; 95% CI, .03-.15; P < .001). CONCLUSIONS: Congenital malaria is an important cause of neonatal morbidity in this region co-endemic for P. falciparum and P. vivax malaria. The introduction of artemisinin-combination therapy was associated with a significant risk reduction in the vertical transmission of malaria.

Congenital malaria in Urabá, Colombia.

BACKGROUND: Congenital malaria has been considered a rare event; however, recent reports have shown frequencies ranging from 3% to 54.2% among newborns of mothers who had suffered malaria during pregnancy. There are only a few references concerning the epidemiological impact of this entity in Latin-America and Colombia. OBJECTIVE: The aim of the study was to measure the prevalence of congenital malaria in an endemic Colombian region and to determine some of its characteristics. METHODS: A prospective, descriptive study was carried out in the mothers who suffered malaria during pregnancy and their newborns. Neonates were clinically evaluated at birth and screened for Plasmodium spp. infection by thick smear from the umbilical cord and peripheral blood, and followed-up weekly during the first 21 days of postnatal life through clinical examinations and thick smears. RESULTS: 116 newborns were included in the study and 80 umbilical cord samples were obtained. Five cases of congenital infection were identified (four caused by P. vivax and one by P. falciparum), two in umbilical cord blood and three in newborn peripheral blood. One case was diagnosed at birth and the others during follow-up. Prevalence of congenital infection was 4.3%. One of the infected newborns was severely ill, while the others were asymptomatic and apparently healthy. The mothers of the newborns with congenital malaria had been diagnosed with malaria in the last trimester of pregnancy or during delivery, and also presented placental infection. CONCLUSIONS: Congenital malaria may be a frequent event in newborns of mothers who have suffered malaria during pregnancy in Colombia. An association was found between congenital malaria and the diagnosis of malaria in the mother during the last trimester of pregnancy or during delivery, and the presence of placental infection.

Congenital and neonatal malaria in a rural Kenyan district hospital: an eight-year analysis.

BACKGROUND: Malaria remains a significant burden in sub-Saharan Africa. However, data on burden of congenital and neonatal malaria is scarce and contradictory, with some recent studies reporting a high burden. Using prospectively collected data on neonatal admissions to a rural district hospital in a region of stable malaria endemicity in Kenya, the prevalence of congenital and neonatal malaria was described. METHODS: From 1st January 2002 to 31st December 2009, admission and discharge information on all neonates admitted to Kilifi District Hospital was collected. At admission, blood was also drawn for routine investigations, which included a full blood count, blood culture and blood slide for malaria parasites. RESULTS: Of the 5,114 neonates admitted during the eight-year surveillance period, blood slide for malaria parasites was performed in 4,790 (93.7%). 18 (0.35%) neonates with Plasmodium falciparum malaria parasitaemia, of whom 11 were admitted within the first week of life and thus classified as congenital parasitaemia, were identified. 7/18 (39%) had fever. Parasite densities were low, ≤50 per µl in 14 cases. The presence of parasitaemia was associated with low haemoglobin (Hb) of <10 g/dl (χ² 10.9 P = 0.001). The case fatality rate of those with and without parasitaemia was similar. Plasmodium falciparum parasitaemia was identified as the cause of symptoms in four neonates. CONCLUSION: Congenital and neonatal malaria are rare in this malaria endemic region. Performing a blood slide for malaria parasites among sick neonates in malaria endemic regions is advisable. This study does not support routine treatment with anti-malarial drugs among admitted neonates with or without fever even in a malaria endemic region.

Clinical presentation of congenital malaria at the Lagos University Teaching Hospital.

BACKGROUND: Congenital malaria has been increasingly documented in endemic regions. It is important to recognize those clinical features that are due to congenital malaria, which if undetected, might worsen the morbidity of the newborn. The aim of this study was to document the clinical presentation of neonates with congenital malaria born at the Lagos University Teaching Hospital and followed up for 28 days. METHODS: A total of 100 consecutive mothers and their newborns were recruited between August and October 2002 (during the rainy season) from the labour ward and followed up from birth to 28 days of age. Blood films from the placentae and babies were stained with Giemsa stain within 24 hours of collection. All parasitaemic babies that became symptomatic were screened for sepsis using acute phase responses and cultures. All data were entered into a prepared proforma. Symptoms were attributed to malaria when sepsis screening was negative. RESULTS: Congenital malaria was documented in 13.6% of babies at delivery. Jaundice, irritability and poor feeding were most common symptoms associated with congenital malaria. Irritability and poor feeding had positive predictive values (PPV) of 100% on Day 14. CONCLUSION: Babies who present with poor feeding and irritability on Day 14 of life should be screened for malaria in addition to the routine investigations for neonatal sepsis.

Severe congenital malaria acquired in utero.

Vertical transmission of Plasmodium falciparum is under-recognized and usually associated with asymptomatic low-level parasitemia at birth. We report symptomatic congenital malaria presenting as a neonatal sepsis syndrome. The presence at birth of a high asexual parasitemia, gametocytemia, and splenomegaly indicated in utero rather than intrapartum transmission. The neonate was successfully treated with intravenous artesunate followed by oral dihydroartemisinin-piperaquine, without apparent adverse effects.

Perinatal malaria and tuberculosis co-infection: a case report.

India remains endemic for both vivax malaria and tuberculosis. In spite of the high burden of tuberculosis in the country, reports on congenital tuberculosis in the literature are limited. We report herein an unusual instance of co-occurrence of perinatal falciparum malaria and tuberculosis in a 34-day-old female newborn, who presented with symptoms of sepsis. The diagnosis was based on the demonstration of Plasmodium falciparum on peripheral blood smear and tubercle bacilli in gastric aspirate samples. The maternal history for falciparum malaria was positive during her eighth month of pregnancy and the father was an open case of sputum smear-positive pulmonary tuberculosis. She responded dramatically to combined antimalarial and antitubercular chemotherapy. A search for combined etiologies in presumed 'sepsis' in the newborn, guided by history, physical examination, and laboratory investigations, is warranted.

The effect of placental malaria infection on cord blood and maternal immunoregulatory responses at birth.

Placental malaria (PM), a frequent infection of pregnancy, provides an ideal opportunity to investigate the impact on immune development of exposure of the foetal immune system to foreign Ag. We investigated the effect of PM on the regulatory phenotype and function of cord blood cells from healthy Gambian newborns and peripheral blood cells from their mothers, and analyzed for effects on the balance between regulatory and effector responses. Using the gold standard for classifying PM we further distinguished between resolved infection and acute or chronic PM active at the time of delivery. We show that exposure to malarial Ag in utero results in the expansion of malaria-specific FOXP3(+) Treg and more generalized FOXP3(+) CD4(+) Treg in chronic and resolved PM, alongside increased Th1 pro-inflammatory responses (IFN-gamma, TNF-alpha, IFN-gamma:IL-10) in resolved PM infection only. These observations demonstrate a clear effect of exposure to malarial Ag in foetal life on the immune environment at birth, with a regulatory response dominating in the newborns with ongoing chronic PM, while those with resolved infection produce both regulatory and inflammatory responses. The findings might explain some of the adverse effects on the health of babies born to women with PM.

Congenital Plasmodium falciparum infection in neonates in Muheza District, Tanzania.

BACKGROUND: Although recent reports on congenital malaria suggest that the incidence is increasing, it is difficult to determine whether the clinical disease is due to parasites acquired before delivery or as a result of contamination by maternal blood at birth. Understanding of the method of parasite acquisition is important for estimating the time incidence of congenital malaria and design of preventive measures. The aim of this study was to determine whether the first Plasmodium falciparum malaria disease in infants is due to same parasites present on the placenta at birth. METHODS: Babies born to mothers with P. falciparum parasites on the placenta detected by PCR were followed up to two years and observed for malaria episodes. Paired placental and infant peripheral blood samples at first malaria episode within first three months of life were genotyped (msp2) to determine genetic relatedness. Selected amplifications from nested PCR were sequenced and compared between pairs. RESULTS: Eighteen (19.1%) out of 95 infants who were followed up developed clinical malaria within the first three months of age. Eight pairs (60%) out of 14 pairs of sequenced placental and cord samples were genetically related while six (40%) were genetically unrelated. One pair (14.3%) out of seven pairs of sequenced placental and infants samples were genetically related. In addition, infants born from primigravidae mothers were more likely to be infected with P. falciparum (P < 0.001) as compared to infants from secundigravidae and multigravidae mothers during the two years of follow up. Infants from multigravidae mothers got the first P. falciparum infection earlier than those from secundigravidae and primigravidae mothers (RR = 1.43). CONCLUSION: Plasmodium falciparum malaria parasites present on the placenta as detected by PCR are more likely to result in clinical disease (congenital malaria) in the infant during the first three months of life. However, sequencing data seem to question the validity of this likelihood. Therefore, the relationship between placental parasites and first clinical disease need to be confirmed in larger studies.

The prevalence of congenital malaria among neonates with suspected sepsis in Calabar, Nigeria.

We studied the prevalence of congenital malaria among neonates with suspected sepsis and its outcome at the University of Calabar Teaching Hospital, Calabar, Nigeria. All in-born neonates admitted to the newborn unit with clinical features suggestive of sepsis were recruited. They were screened for bacterial sepsis and malaria. The mothers of the neonates that had parasitaemia were further screened for malaria and anaemia. A total of 546 in-born neonates were admitted to the neonatal unit and 202 (37%) presented with clinical signs suggested of sepsis. Of these, 71 babies (35% of 202 or 13% of the total in-born nursery admissions) had congenital malaria and 14 also had sepsis. Sixty-three (88.7%) of the parasitaemic babies were delivered by mothers who received antenatal care at our centre. Eighty-six percent of the mothers of the 71 babies also had the malaria parasite in their blood. The majority (67%) of the 71 mothers were gravidae 2 and below. Thirty (42.3%) of the affected neonates were anaemic and 5 (7%) of them required a blood transfusion. Congenital malarial is not uncommon in Calabar among babies with suspected sepsis. It appears that the antenatal chemoprophylaxis with pyrimethamine (25 mg weekly) currently used for malaria in our centre no longer protects the mother and fetus. An alternative is needed in order to stem maternal, fetal and neonatal morbidity and wastage. Babies with features of sepsis should be routinely screened for malaria.

Possible risk factors for congenital malaria at a tertiary care hospital in Sagamu, Ogun State, South-West Nigeria.

Congenital malaria, defined as the presence of malaria parasites in the erythrocytes of newborns aged <7 days, was considered rare in endemic areas until recent studies started reporting high prevalence rates. Various theories have been postulated to explain this phenomenon, but they are not proven conclusively from research. Against this background, a prospective study was designed with the following objectives. To determine the prevalence of congenital malaria parasitaemia and identify possible risk factors amongst newborns delivered in O.O.U.T.H Sagamu, Ogun State. Over a 6-month period, 192 live newborns and their mothers were consecutively recruited into the study. Within 3 days of life, neonatal peripheral blood samples were collected for malaria screening by blood film microscopy and detection of plasmodium lactate dehydrogenase (pLDH) with the OptiMAL Rapid Malaria Test kit. Maternal peripheral blood samples were taken simultaneously, to check for malaria infestation by blood film microscopy, and questionnaires were administered on the mothers to identify possible factors associated with the development of neonatal parasitaemia. Neonatal clinical and laboratory data were recorded in a pro forma designed for the study. Data analysis was done with Epi-info version 6 software and level of significance set at <5%. Twenty-one of 192 newborns delivered in O.O.U.T.H within the study period were diagnosed as having congenital malaria by blood film microscopy, giving a prevalence rate of 10.9%. The main identified innate neonatal risk factor for congenital malaria parasitaemia was prematurity. First-order pregnancy, history of fever within 3 months of delivery and peripheral parasitaemia at delivery (p < 0.001) were the variables that were significantly higher in the mothers of the parasitemic newborns. We conclude that congenital malaria parasitaemia in tropical endemic areas is not rare. Pre-term neonates, infants of primigravidae, women with history of fever within 3 months of delivery and women with post-partum peripheral parasitaemia may benefit from routine screening for malaria.