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Infectious diseases
The literature devoted to infectious diseases in pregnancy is often sparse and out of date. The Pregnant Traveler, as an organization, is seeking to gradually remedy this situation as we are in the process of preparing and publishing a series of journal articles regarding the interplay of pregnancy and various infectious diseases. (Watch our CV for these articles as they are published.) Meanwhile, we will try to present those references that we have found useful.
General
1. ACOG Educational Bulletin #245—Antimicrobial Therapy for Obstetric Patients
2. ACOG Practice Bulletin #20—Perinatal Viral and Parasitic Infections
3. Cline MK, Bailey-Dorton C, Cayelli M. Maternal infections: diagnosis and management. Prim Care 2000 Mar;27(1):13-33. An understanding of the common infections that occur during pregnancy is crucial for prenatal care providers. This article discusses specific screening and diagnostic tests, along with appropriate treatment regimens for common bacterial, viral, protozoal, and fungal infections that occur during pregnancy. Additionally, methods to reduce the likelihood of infection, such as preconception immunization, are reviewed.
Typhoid
1. Carles G, Montoya Y, Seve B, Rakotofananina T, Largeaud M, Mignot V. Typhoid fever and pregnancy. J Gynecol Obstet Biol Reprod (Paris). 2002 Sep;31(5):495-9 [Article in French]. Typhoid fever is rare in Europe, but well-recognized endemic disease in tropical zones. We report our findings in a series of 25 cases of typhoid fever during pregnancy observed in French Guiana and reviewed the literature on clinical signs, diagnosis and treatment. Salmonellea typhi causes septicemia of digestive origin that can cross the placenta resulting in chorioamniotitis. Maternal-fetal infection with S. typhi can lead to miscarriage, fetal death, neonatal infection, as well as diverse maternal complications. In order to avoid maternal complications and possible fetal transmission, treatment with ceftriaxone should be initiated as early as possible. 2. Figueroa Damian R, Segura Cervantes E, Garcia Arce T, de la Cruz Bolaanos R. Typhoid fever in pregnancy. Clinical course, treatment and perinatal repercussions. Ginecol Obstet Mex. 1994 Nov;62:362-7. [Article in Spanish] In Mexico typhoid fever (TF) is still a disease of major importance. The reports of TF complicating pregnancy are few in number, nevertheless the majority of authors agree than pregnancy does not alter the clinical presentation or the laboratory findings of the patient with TF. In these cases data suggest unfavorable perinatal outcome with a greater frequency of abortions and premature delivery. We report five cases of TF complicating pregnancy; one patient aborted, one had a preterm labor with neonatal dead of the product, and the other three had a normal pregnancy without abnormalities of the newborns. An improved outcome of the pregnant women complicated with TF is associated with a proper diagnosis and early treatment with ampicillin of ceftriaxone. Chloramphenicol is contraindicated during pregnancy.
Malaria
1. Nahlen BL. Rolling Back Malaria in Pregnancy NEJM 2000;343:9
2. Matteelli A, Caligaris S, Castelli F, Carosi G. The placenta and malaria. Ann Trop Med Parasitol 1997 Oct;91(7):803-10. Placental malaria is recognized as a common complication of malaria in pregnancy in areas of stable transmission, and is particularly frequent and severe in primigravidae. Many hypotheses, based on a systemic or local failure of the immunological response to malaria, have been proposed to explain the 'preference' of the parasites for replication in the placenta. Some of the hypotheses are briefly reviewed here, with a particular focus on the discovery of an uncommon subpopulation of Plasmodium falciparum which can adhere and massively sequester in the placenta. Histologically, placental malaria is characterized by the presence of parasites and leucocytes within the intervillous spaces, pigment within macrophages, fibrin deposits and trophoblasts, proliferation of cytotrophoblastic cells and thickening of the trophoblastic basement membrane. The exact mechanisms leading to placental changes and determining the observed impairment of materno-foetal exchange are incompletely understood. Parasites are unlikely to be directly responsible for the placental pathology, but leucocytes, through the production of non-chemotactic cytokines, might be associated with the thickening of the trophoblastic basement membrane, and might cause a mechanical blockage of oxygen and nutrient transport across the placenta. There is sound epidemiological evidence that placental malaria determines low birthweight, mainly mediated by intrauterine growth retardation, and increases the risk of death and disease during the first year of life. Antimalarial chemoprophylaxis significantly reduces placental malaria and prevents the development of low birthweight. It is likely that, in areas of high endemicity, the placenta is where the drama of maternal malaria is mostly played. A deeper understanding of the mechanisms involved in this process is of key importance in the design of protective interventions which are effective and acceptable during the gestation period.
3. Lindsay S, Ansell J, Selman C. Effect of pregnancy on exposure to malaria mosquitoes. Lancet 2000;355:1972. Pregnant women attracted twice the number of Anopheles gambia complex—the predominant African malaria-carrying mosquito—than did their non-pregnant counterparts. We postulate that physiological and behavioural changes that occur during pregnancy are responsible for increased attractiveness, which could be important in intervention strategies aimed at protecting this high-risk group against malaria.
4. Ansell J, Hamilton KA, Pinder M, Walraven GE, Lindsay SW. Short-range attractiveness of pregnant women to Anopheles gambiae mosquitoes. Trans R Soc Trop Med Hyg. 2002 Mar-Apr;96(2):113-6. Malaria is a major cause of illness and an indirect cause of mortality in pregnant women. It can also cause stillbirths and low-birthweight babies. We have shown previously that pregnant women attracted twice as many Anopheles gambiae mosquitoes, the principal African malaria vector, as their non-pregnant counterparts over distances of about 15 m. In the current study (in 1998/99) we compared the short-range attractiveness of both pregnant and non-pregnant women sleeping under untreated bednets in Gambian villages. First, we measured the rate of mosquito entry under bednets and, second, we calculated the proportion of mosquitoes biting mothers under each bednet compared to their children. The feeding preference of An. gambiae collected under nets was determined by DNA fingerprinting blood samples from human subjects sleeping under each bednet and comparing these to fingerprints obtained from mosquito bloodmeals. Pregnant women were more attractive to An. gambiae mosquitoes than non-pregnant women under an untreated bednet. The number of mosquitoes entering bednets each night was 1.7-4.5 times higher in the pregnant group (P = 0.02) and pregnant women also received a higher proportion of bites under the bednets than did non-pregnant women (70% vs 52%, P = 0.001). This study clearly demonstrates that pregnant women are more exposed to malaria parasites than other women, which contributes to the greater vulnerability of pregnant women to malaria.
5. Singh N, Shukla MM, Sharma VP. Epidemiology of malaria in pregnancy in central India. Bull World Health Organ 1999;77(7):567-72. Analysis of three years of data from a malaria clinic operated by the Indian Council of Medical Research (ICMR) in the Government Medical College Hospital in Jabalpur, central India, showed a high malaria prevalence among pregnant women, which was statistically highly significant (P < 0.0001) compared with the situation among nonpregnant women. Cerebral malaria was a common complication of severe Plasmodium falciparum infection, with a high mortality during pregnancy, requiring immediate attention. The study also showed that malaria infection was more frequent in primigravidae, falling progressively with increasing parity. Mean parasite densities were significantly higher in pregnant women compared with nonpregnant women for both P. falciparum (P < 0.001; df = 137) and P. vivax (P < 0.05; df = 72) infection. Pregnant women with falciparum or vivax malaria were significantly more anaemic than noninfected pregnant women or infected nonpregnant women. The average weight of 155 neonates from infected mothers was 350 g less than that of 175 neonates from noninfected mothers. This difference in birth weight was statistically significant for both P. falciparum (P < 0.0001; df = 278) and P. vivax (P < 0.0001; df = 223) infection. Congenital malaria was not recorded. We conclude that pregnant women from this geographical area require systematic intervention owing to their high susceptibility to malaria during pregnancy and the puerperium.
6. Garner P, Gulmezoglu AM. Prevention versus treatment for malaria in pregnant women. Cochrane Database Syst Rev 2000;(2):CD000169
7. Shulman CE. Malaria in pregnancy: its relevance to safe-motherhood programmes. Ann Trop Med Parasitol 1999 Dec;93 Suppl 1:S59-66
8. Davis TM, Suputtamongkol Y, Spencer JL, Wilson SG, Mekhton S, Croft KD, White NJ Glucose turnover in pregnant women with acute malaria. Clin Sci (Colch) 1994 Jan;86(1):83-90. Hypoglycaemia is a serious complication of falciparum malaria, especially in pregnant patients. To investigate malaria-associated changes in glucose metabolism in pregnancy, steady-state [6,6-2H2] glucose turnover and clearance were measured in 10 women (eight with uncomplicated falciparum malaria and two with vivax malaria at 16-30 weeks gestation) before treatment, after intravenous quinine infusion (patients with falciparum malaria) and in convalescence. 2. Admission basal plasma glucose concentrations were higher than those in convalescence [median (range); 4.8 (3.6-7.0) versus 4.0 (3.6-4.6) mmol/l, P = 0.02], and there was a significant fall during initial quinine treatment in patients with falciparum malaria [5.0 (4.3-7.6) to 3.6 (3.2-5.4) mmol/l, P < 0.01]. Basal plasma insulin levels were comparable at presentation and follow-up (P = 0.35) and rose an average of only 2m-units/l during quinine infusion (P < 0.05). Pretreatment glucose turnover rates [3.37 (2.57-4.16) mg min-1 kg-1] were comparable with those found in a previously reported study of non-pregnant severely ill patients [3.22 (2.12-4.82) mg min-1 kg-1, n = 11] and correlated significantly with the admission parasitaemia (P < 0.025). In the eight patients with falciparum malaria, there was a significant fall in turnover during intravenous quinine infusion [3.42 (2.58-4.16) to 2.66 [1.94-3.94) mg min-1 kg-1] whereas clearance did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
9. Diagne N, Rogier C, Sokhna CS, et al. Increased Susceptibility to Malaria during the Early Postpartum Period NEJM 2000;343:9. Abstract Background. Pregnancy is associated with increased susceptibility to malaria. It is generally agreed that this increased risk ends with delivery, but the possible persistence of increased susceptibility during the puerperium has not been investigated. Methods. From June 1, 1990, to December 31, 1998, we monitored exposure to malaria, parasitemia, and morbidity among the residents of a village in Senegal in which the rate of transmission of malaria was high. In this population we analyzed 71 pregnancies in 38 women from the year before conception through one year after delivery. Results. Among the 38 women, there were 58 episodes of clinical Plasmodium falciparum malaria during 61,081 person-days of observation. The incidence of malaria was 20.2 episodes per 1000 person-months during the year preceding conception and 12.0 episodes per 1000 person-months during the period from 91 to 365 days after delivery. The incidence of episodes of malaria increased significantly during the second and third trimesters of pregnancy and reached a maximum of 75.1 episodes per 1000 person-months during the first 60 days after delivery. The adjusted relative risk of an episode of malaria was 4.1 (95 percent confidence interval, 1.8 to 9.5) during the first 60 days post partum, as compared with the year preceding pregnancy. The duration of fever during the episodes of malaria was longer and the prevalence and density of asymptomatic malarial parasitemia were significantly higher during pregnancy and the early postpartum period than during the other periods. Conclusions. Among women who live in areas with high rates of transmission of malaria, the susceptibility to malaria is highest during the second and third trimesters of pregnancy and the early postpartum period.
10. Boulos M, Costa JM, Tosta CE Pulmonary involvement in malaria. Rev Inst Med Trop Sao Paulo 1993 Jan-Feb;35(1):93-102
11. Tian LP, Nelson EA, Senok AC, Yu LM, Oppenheimer SJ, Li K. Red cell age and susceptibility to malaria during pregnancy. Acta Obstet Gynecol Scand 1998 Aug;77(7):717-21
12. The Working Group for Malaria Prophylaxis, Malaria prophylaxis; advice for the individual traveller. Ned Tijdschr Geneeskd 1998 Apr 18;142(16):912-4
13. Taha TE . Comparison of reported and confirmed malaria during pregnancy: findings from hospital and community studies in Sudan. East Afr Med J 1996 Sep;73(9):571-4
14. Silver HM. Malarial infection during pregnancy. Infect Dis Clin North Am 1997 Mar;11(1):99-107 This article reviews the parasitology of malaria, epidemiology in pregnancy, pathogenesis of increased susceptibility to infection in pregnancy, the effect of pregnancy on the clinical manifestations of malaria, the effect of malaria on perinatal outcomes, the safety of antimalarial agents during pregnancy, the role of chemoprophylaxis for inhabitants and travelers to endemic areas, and treatment of clinical malarial infections during pregnancy.
15. Baud M, Bauchet E, Poilane I, Levacher S, Pourriat JL. Acute respiratory distress syndrome due to falciparum malaria in a pregnant woman. Intensive Care Med 1997 Jul;23(7):787-9 UI97436328
16. Bukman A, Weinans MJ, van Loon AJ. Severe Plasmodium falciparum malaria in a non-immune pregnant woman. Int J Gynaecol Obstet 1997 Nov;59(2):143-4
17. Shulman CE. Malaria in pregnancy: its relevance to safe-motherhood programmes. Ann Trop Med Parasitol 1999 Dec;93 Suppl 1:S59-66
18. Verhoeff FH, Brabin BJ, Chimsuku L, Kazembe P, Broadhead RL. Malaria in pregnancy and its consequences for the infant in rural Malawi. Ann Trop Med Parasitol 1999 Dec;93 Suppl 1:S25-33
19. Nosten F, McGready R, Simpson JA, Thwai KL, Balkan S, Cho T, Hkirijaroen L, Looareesuwan S, White NJ. Effects of Plasmodium vivax malaria in pregnancy. Lancet 1999 Aug 14;354(9178):546-9. BACKGROUND: Plasmodium vivax is more common than P. falciparum as a cause of malaria in many parts of the tropics outside Africa. P. falciparum infection has harmful effects in pregnancy, but the effects of P. vivax have not beencharacterised. We investigated the effects of P. vivax infection during pregnancy. METHODS: Since 1986, pregnant Karen women living in camps for displaced people on the western border of Thailand have been encouraged to attend antenatal clinics. Karen women were screened for malaria and anaemia at each week of pregnancy until delivery, and pregnancy outcome recorded. We compared the effects of P. vivax infection on anaemia and pregnancy outcome with those of P. falciparum and no malaria infection in the first pregnancy recorded at the antenatal clinics. FINDINGS: There were 634 first episodes of pure P. vivax malaria in 9956 women. P. vivax malaria was more common in primigravidae than in multigravidae and was associated with mild anaemia and an increased risk of low birthweight (odds ratio 1.64 [95% CI 1.29-2.08], p<0.001). The birthweight was a mean of 107 g (95% CI 61-154) lower in women with P. vivax infection than in uninfected women. By contrast with P. falciparum malaria, the decrease in birthweight was greater in multigravidae. P. vivax malaria was not associated with miscarriage, stillbirth, or with a shortened duration of pregnancy. INTERPRETATION: P. vivax malaria during pregnancy is associated with maternal anaemia and low birthweight. The effects of P. vivax infection are less striking than those of P. falciparum infection, but antimalarial prophylaxis against P. vivax in pregnancy may be justified.
20. Alecrim WD, Espinosa FE, Alecrim MG, Plasmodium falciparum infection in the pregnant patient. Infect Dis Clin North Am 2000 Mar;14(1):83-95, viii-ix. Malaria should be considered a risk factor in women who are pregnant, principally when the infection is Plasmodium falciparum. Moreover, the risk is greater if the woman is pregnant for the first time; if she has no immunity for malaria; if the diagnosis is made late; or if P. falciparum shows resistance to antimalarial drugs. This article presents the most significant aspects of P. falciparum malaria during pregnancy, including information about treatments and prophylaxis.
21. Bruce-Chwatt LJ. Malaria and pregnancy. BMJ 1983;286:1457-8.
22. McGregor IA, Wilson ME, Billewicz WZ. Malaria infection of the placenta in The Gambia, west Africa: its incidence and relationship to stillbirth, birth weight and placental weight. Trans R Soc Trop Med Hyg 1983;77:232-44.
23. Rietveld AE. Malaria prevention for special groups : pregnant women, infants and young children. In P. Schlagenhauf Ed. Travelers’s malaria. BC Decker Inc Hamilton. 2001:303-323. ABSTRACT During pregnancy or when traveling with infants and young children, it is preferable to completely avoid travel to areas with chloroquine-resistant Plasmodium falciparum malaria. At times, however, that is not possible; in such instances, there are no totally safe and effective preventive measures, and difficult choiceshave to be made. This chapter describes why young children and pregnant travelers are at special risk of malaria and lays out the currently available options and safety aspects of chemoprophylaxis and personal protection measures for these high-risk groups. Falciparum malaria in infants, young children, and pregnant women is a medical emergency. The rapid progression of clinical symptoms carries the risk of severe disease, fetal loss, and death. Key practical points for the prevention, early diagnosis, and management of malaria in pregnant travelers and in early childhood are provided.
24. Steketee RW, Wirima JJ, Hightower AW, Slutsker L, Heymann DL, Breman JG The effect of malaria and malaria prevention in pregnancy on offspring birthweight, prematurity, and intrauterine growth retardation in rural Malawi. Am J Trop Med Hyg 1996;55(1 Suppl):33-41. 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.
Parasites
1. Liu LX, Weller PF. Strongyloidiasis and other intestinal nematode infections. Infect Dis Clin North Am 1993 Sep;7(3):655-82
2. Kain KC, Keystone JS. Recurrent hydatid disease during pregnancy. Am J Obstet Gynecol 1988 Nov;159(5):1216-7 A Syrian woman with pulmonary and hepatic Echinococcus granulosus had symptoms of hydatid disease during each of three consecutive pregnancies. We postulate that the decrease in cellular immunity that accompanies pregnancy might allow for increased parasite growth. Obstetricians should be aware of the potential during pregnancy for rapid progression and complications of hydatid disease.
3. Guderian RH, Lovato R, Anselmi M, Mancero T, Cooper PJ. Onchocerciasis and reproductive health in Ecuador. Trans R Soc Trop Med Hyg 1997 May-Jun;91(3):315-7. A retrospective study was performed comparing the number of spontaneous abortions in a hyperendemic area for onchocerciasis in Ecuador before and after invermectin treatment with that of a comparable non-endemic area. The frequency of spontaneous abortions was associated with a change in the community microfilarial load, suggesting that there may be a relationship between spontaneous abortions and infection with Onchocerca volvulus. In the endemic area, a significantly greater rate of spontaneous abortions was seen in the period before ivermectin distribution compared to that after the start of ivermectin treatments every 6 months. In the non-endemic area, no change in the rate of spontaneous abortions was seen over the same time period. In addition to the well-documented improvements in skin and ocular disease, ivermectin may also improve the reproductive health of endemic populations.
4. Alexander ND, Grenfell BT. The effect of pregnancy on Wuchereria bancrofti microfilarial load in humans. Parasitology 1999 Aug;119 ( Pt 2):151-6. As part of a drug trial against bancroftian filariasis in the East Sepik Province of Papua New Guinea we measured the pre-treatment microfilarial densities of 2219 individuals. Mean levels generally increased with age in both sexes, with a tendency to plateau at the highest ages. However, there was a reduction among women of approximately reproductive age. Allowing for the tendency for aggregation to decrease with age, this reduction was statistically significant. However, a comparison of pregnant women and controls showed no evidence that the reduction is specifically related to pregnancy. Moreover, a simple differential equation model of microfilarial acquisition and loss suggests that age-specific patterns of exposure are also unlikely to be solely responsible. Therefore, we suggest that the observed reduction in microfilarial intensity may result from hormonal changes associated with female reproduction, possibly in combination with other factors.
5. Bialek R, Knobloch J. [Parasitic infections in pregnancy and congenital parasitoses. II. Helminth infections]. Z Geburtshilfe Neonatol 1999 May-Jun;203(3):128-33 [Article in German]. The main sequela of helminthic infections is anemia, causing increased perinatal mortality and morbidity worldwide. During pregnancy symptomatic treatment is usually sufficient to control the disease. The specific and very effective treatment with albendazole, mebendazole, ivermectin and praziquantel has embryo-, fetotoxic, mutagenic and teratogenic potential. Therefore, it should be delayed until after delivery. In some cases immediate specific therapy might be mandatory. Congenital helminthic infection in humans is a rarely described event.
6. Soboslay PT, Geiger SM, Drabner B, Banla M, Batchassi E, Kowu LA, Stadler A, Schulz-Key H. Prenatal immune priming in onchocerciasis-onchocerca volvulus-specific cellular responsiveness and cytokine production in newborns from infected mothers. Clin Exp Immunol 1999 Jul;117(1):130-7. This study investigated the effect of maternal Onchocerca volvulus infection on humoral and cellular responsiveness in newborn children and their mothers. Onchocerca volvulus-specific IgG isotypes and IgE were significantly elevated in infected mothers and their infants. One year post partum, O. volvulus-specific IgG4 was strongly reduced in children of infected mothers, while IgG1 responses weakened only slightly. Umbilical cord mononuclear blood cells (UCBC) and peripheral blood cells (PBMC) from mothers proliferated in response to phytohaemagglutinin (PHA), concanavalin A (Con A), and the bacterial antigens streptolysin-O (SL-O) or purified protein derivative (PPD). UCBC from neonates born to O. volvulus-infected mothers responded lower (P < 0.01) to Con A (at 5 micrograms/ml), PPD (at 10 and 50 micrograms/ml) and O. volvulus-derived antigens (OvAg) (at 35 micrograms/ml), and in parallel, a diminished cellular reactivity (P < 0.01) by PBMC was observed to OvAg in mothers positive for O. volvulus. Several Th1-type (IL-2, IL-12, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha)) and Th2-type (IL-4, IL-5, IL-10, IL-13) cytokines were secreted by UCBC and PBMC in response to OvAg, bacterial SL-O and PHA. OvAg did not stimulate IL-2 and none of the mitogens or antigens induced production of IL-4 in neonates. In response to OvAg, substantially elevated (P < 0.01) amounts of IFN-gamma were produced by UCBC from newborns of O. volvulus-infected mothers. UCBC secreted low levels of IL-5 and IL-13, while higher amounts of IL-10 were found (P < 0. 01) in newborns from onchocerciasis-free mothers. In conclusion, maternal O. volvulus-infection will sensitize in utero parasite-specific cellular immune responsiveness in neonates and activate OvAg-specific production of several Th1- and Th2-type cytokines.
7. Nouhou H, Seve B, Idi N, Moussa F [Schistosomiasis of the female genital tract: anatomoclinical and histopathological aspects. Apropos of 26 cases]. [Article in French] Bull Soc Pathol Exot 1998;91(3):221-3. The authors report 26 cases of female genital schistosomiasis. This parasitosis is observed in women of ages ranging between 17 and 70 years (mean age = 30 years) and associated with sterility (6 cases), uterine tract cancer (1 case), tubular pregnancy (1 case), benign teratoma (1 case) and serous cystadenoma (1 case). The diagnosis is based on an histological analysis which shows several lesions with schistosomiasis (Schistosoma haematobium) eggs, confirmed by ZIEHL coloration. When coupled with infections these anatomical lesions lead to dysfunctions such as sterility and extra-uterine pregnancy through tubular dysfunction.
8. Navitsky RC, Dreyfuss ML, Shrestha J, Khatry SK, Stoltzfus RJ, Albonico M. Ancylostoma duodenale is responsible for hookworm infections among pregnant women in the rural plains of Nepal. J Parasitol 1998 Jun;84(3):647-51. Fecal specimens from 292 pregnant women (ages 15-40 yr) and 129 infants (ages 10-20 wk) were examined for helminth eggs by the Kato-Katz method and cultured for helminth larvae identification using a modified Harada Mori method. These specimens were collected from June 1995 through July 1996 in Sarlahi District in the southern rural plains of Nepal. Among pregnant women, the prevalence of helminth infection by the Kato-Katz method was 78.8%, 56.2%, and 7.9% for hookworm, Ascaris lumbricoides, and Trichuris trichiura, respectively. Using the modified Harada-Mori method, 66.1% and 2.0% of women's fecal cultures were positive for hookworm and Strongyloides stercoralis, respectively. All of the cultured hookworm larvae were identified as Ancylostoma duodenale. Among infants, 1 specimen was positive for hookworm and 1 for A. lumbricoides using the Kato-Katz method. The modified Harada Mori method detected no larvae in specimens from infants. There was 81.8% agreement between the 2 methods for the detection of hookworm infection. Ancylostoma duodenale is endemic in this study population and highly prevalent in pregnant women.
9. Hassan MM, Hassounah OA, Hegab M, Salah K, el-Mahrouky L, Galal N Transmission of circulating schistosomal antigens from infected mothers to their newborns. J Egypt Soc Parasitol 1997 Dec;27(3):773-80. Two previous reports have appeared in the literature regarding tansplacental transfer of Schistosoma mansoni antigens which raised the question of its reality. In a previous study the senior author, and others (1992 & 1997) detected circulating antigens of S. mansoni and S. haematobium in infected patients, using monoclonal antibodies 128C3, with a very high sensitivity using ELISA. This work tried to answer the question of antigen transfer possibility using a high sensitive assay in 50 mothers and their newborns at birth and 1, 3, and 6 months after delivery. The assay used in the present work could detect\ circulating S. mansoni antigens in 45 infected mothers (90%) with active S. mansoni infection. A significant direct increase in mean antigen levels was found with the intensity of infection evaluated by egg counting (p < 0.01). The clinical stage of the diseased mothers was apparently unrelated to the ELISA test values as no significant relations were observed. Positive antigen levels were detected in 33 newborns (66%) of the 45 positive antigen mothers, then the percentage positivity was directly decreased with the advancement of age as only 5 infants (10%) had positive antigen levels compared to 0% at 6 months of age. A positive correlation between newborn serum antigen concentration and concentration of antigen in sera of their mothers was obtained. This work answers some of the questions concerning the ability of the used monoclonal to detect antigens in newborns and the possibility of antigen transfer through the placenta alone or incorporated in immune complexes forms. This work clarifies the time of antigen disappearance from the circulation.
10. de Silva N, Guyatt H, Bundy D. Anthelmintics. A comparative review of their clinical pharmacology. Drugs 1997 May;53(5):769-88. Virtually all the important helminth infections in humans can be treated with one of 5 anthelmintics currently in use: albendazole, mebendazole, diethylcarbamazine, ivermectin and praziquantel. These drugs are vital not only for the treatment of individual infections, but also useful in controlling transmission of the more common infections. This article reviews briefly the pharmacology of these 5 drugs, and then discusses current issues in the use of anthelmintics in the treatment and/or control of soil-transmitted nematode infections, filariasis, onchocerciasis, schistosomiasis (and other trematode infections), neurocysticercosis and hydatidosis. Mebendazole and albendazole are most effective against intestinal nematodes, but are contraindicated during the first trimester of pregnancy. The efficacy of prolonged therapy with these 2 drugs for treatment of larval cestode infections has not yet been established. Diethylcarbamazine is widely used to treat and control lymphatic filariasis, but adverse effects related to death of microfilariae or damage to adult worms may be marked. While ivermectin has been used in the treatment of patients with onchocerciasis, it is also undergoing investigation against lymphatic filariae. Praziquantel, used to treat schistosome infections, is also effective in other trematode infections and adult cestode infections.
11. Asrat T, Rogers N. Acute pancreatitis caused by biliary ascaris in pregnancy. J Perinatol 1995 Jul-Aug;15(4):330-2. Ascaris lumbroicoides is the most prevalent human parasite worldwide. Although usually asymptomatic, ascaris is responsible for a variety of severe complications such as intestinal obstruction, cholangitis, or hepatitis, which are caused by worm migration. This article is the second known case report of pancreatitis caused by biliary ascaris during pregnancy. We also review the pathophysiology of this disease and review the various treatment modalities available for pregnant patients. We believe that because of the growing influx of immigrants from endemic areas into the United States, the clinician needs a basic understanding of the etiology, diagnosis, and treatment of biliary ascarasis.
12. Hamblin J, Connor PD. Pinworms in pregnancy. J Am Board Fam Pract 1995 Jul-Aug;8(4):321-4.
13. Okonofua FE, Ojo OS, Odunsi OA, Odesanmi WO. Ectopic pregnancy associated with tubal schistosomiasis in a Nigerian woman. Int J Gynaecol Obstet 1990 Jul;32(3):281-4. A case of ruptured tubal ectopic pregnancy is presented. On histological examination of the fallopian tube involved, ova of Schistosoma haematobium were found in the submucosal and intramural parts of the tube. The case illustrates a rare preventable cause of ectopic pregnancy in this population.
14. Mendoza E, Jorda M, Rafel E, Simon A, Andrada E. Invasion of human embryo by Enterobius vermicularis. Arch Pathol Lab Med 1987 Aug;111(8):761-2. Two Enterobius vermicularis organisms invading a macerated embryo 2 cm in length were found in the tissue from an endometrial curettage performed for missed abortion in a pregnant woman. Ova from the helminths were recovered from the vagina and endometrium of the patient. This most unusual case provides further evidence for the invading capacity of E vermicularis.
15. Jenum PA, Stray-Pedersen B, Melby KK, Kapperud G, Whitelaw A, Eskild A, Eng J. Department of Bacteriology, National Institute of Public Health, Oslo, Norway. Incidence of Toxoplasma gondii infection in 35,940 pregnant women in Norway and pregnancy outcome for infected women. J Clin Microbiol. 1998 Oct;36(10):2900-6. From 1992 to 1994 a screening program for detection of specific Toxoplasma gondii antibodies involving 35,940 pregnant women was conducted in Norway. For women with serological evidence of primary T. gondii infection, amniocentesis and antiparasitic treatment were offered. The amniotic fluid was examined for T. gondii by PCR and mouse inoculation to detect fetal infection. Infants of infected mothers had clinical and serological follow-up for at least 1 year to detect congenital infection. Of the women 10.9% were infected before the onset of pregnancy. Forty-seven women (0.17% among previously noninfected women) showed evidence of primary infection during pregnancy. The highest incidence was detected (i) among foreign women (0.60%), (ii) in the capital city of Oslo (0.46%), and (iii) in the first trimester (0.29%). Congenital infection was detected in 11 infants, giving a transmission rate of 23% overall, 13% in the first trimester, 29% in the second, and 50% in the third. During the 1-year follow-up period only one infant, born to an untreated mother, was found to be clinically affected (unilateral chorioretinitis and loss of vision). At the beginning of pregnancy 0.6% of the previously uninfected women were falsely identified as positive by the Platelia Toxo-IgM test, the percentage increasing to 1.3% at the end of pregnancy. Of the women infected prior to pregnancy 6.8% had persisting specific immunoglobulin M (IgM). A positive specific-IgM result had a low predictive value for identifying primary T. gondii infection.
Viruses
1. Yanez Maldonado E, San Martin Herrasti JM, Garcia Alonso A, Izquierdo Puente JC.. [Non-immunologic hydrops. Report of 2 cases]. Ginecol Obstet Mex 2000 Jul;68:282-5. [Article in Spanish]
2. Timuragaoglu A, Surucu F, Nalcaci M, Dincol G, Pekcelen Y.. Anemia and thrombocytopenia due to parvovirus B-19 infection in a pregnant woman. J Med 1997;28(3-4):245-9
3. Sodja I, Mrazova M, Smelhausova M, Uhlir M, Kotrbova K, Pazdiora P, Bruj J, Kadlecik D. [Parvovirus B 19 in pregnancy]. Epidemiol Mikrobiol Imunol 1996 Dec;45(4):143-7 [Article in Czech]
4. Eiros JM, Bachiller R, Martin JF, Bayon E, de Lejarazu RO, Torres AR.. [Infection by parvovirus B-19 and pregnancy]. J Gynecol Obstet Biol Reprod (Paris) 1994;23(2):209. [Article in French]
5. Humphrey W, Magoon M, O'Shaughnessy R.. Severe nonimmune hydrops secondary to parvovirus B-19 infection: Spontaneous reversal in utero and survival of a term infant. Obstet Gynecol 1991 Nov;78(5 Pt 2):900-2
6. Kuhlmann RS, Autry AM. An approach to nonbacterial infections in pregnancy. Clinics in Family Practice. Volume 3 • Number 2 • June 2001
Hepatitis
1. Smith JL.. A review of hepatitis E virus. J Food Prot 2001 Apr;64(4):572-586. Hepatitis E virus (HEV) is a major cause of outbreaks and sporadic cases of viral hepatitis in tropical and subtropical countries but is infrequent in industrialized countries. The virus is transmitted by the fecal-oral route with fecally contaminated drinking water being the usual vehicle. Hepatitis resulting from HEV infection is a moderately severe jaundice that is self-limiting in most patients. Young adults, 15 to 30 years of age, are the main targets of infection, and the overall death rate is 0.5 to 3.0%. However, the death rate during pregnancy approaches 15 to 25%. Death of the mother and fetus, abortion, premature delivery, or death of a live-born baby soon after birth are common complications of hepatitis E infection during pregnancy. Hepatitis E virus is found in both wild and domestic animals; thus, HEV is a zoonotic virus. The viruses isolated from swine in the United States or Taiwan are closely related to human HEV found in those areas. The close genetic relationship of the swine and human virus suggests that swine may be a reservoir of HEV. In areas where swine are raised, swine manure could be a source of HEV contamination of irrigation water or coastal waters with concomitant contamination of produce or shellfish. Increasing globalization of food markets by industrialized countries has the potential of introducing HEV into new areas of the world. The purpose of this review is to cover certain aspects of hepatitis E including the causative agent, the disease, diagnosis, viral detection, viral transmission, epidemiology, populations targeted by HEV, and the role of animals as potential vectors of the virus.
2. Elinav E, Ben-Dov IZ, Shapira Y, Daudi N, Adler R, Shouval D, Ackerman Z Acute hepatitis A infection in pregnancy is associated with high rates of gestational complications and preterm labor.Gastroenterology. 2006 Apr;130(4):1129-34.
BACKGROUND & AIMS: Hepatitis A virus (HAV) infection is the most common cause of acute hepatitis but is rarely reported during pregnancy. Our aim was to evaluate the impact of acute HAV infection on pregnancy outcome. METHODS: Consecutive admissions of 79,458 pregnant females during a 25-year period were retrospectively reviewed. RESULTS: Thirteen cases of second and third trimester HAV infection were found and evaluated. Nine of the 13 patients (69%) developed gestational complications, including premature contractions (n = 4), placental separation (n = 2), premature rupture of membranes (n = 2), and vaginal bleeding (n = 1). In 8 of these patients, complications led to preterm labor, at a median of 34 gestational weeks (range, 31-37 weeks). Delivery was vaginal in 12 of the 13 cases; fetal distress was noted in a single case, and meconium in amniotic fluid in 2 cases. Median birth weight was 1778 grams and 3040 grams in preterm and term deliveries, respectively (P < .05). Child outcome was favorable in all cases. In 4 cases, neonatal serum HAV RNA levels were measured and found negative. The presence of fever and hypoalbuminemia were associated with delivery at an earlier gestational week. There was a positive relation between gestational week at diagnosis of HAV infection and birth week (r = 0.68, P = .02), suggesting a causality relationship. All mothers featured full recovery from HAV infection. CONCLUSIONS: Acute HAV infection during pregnancy is associated with high risk of maternal complications and preterm labor. HAV serology and maternal vaccination during prepregnancy evaluation should be considered in areas of the world in which susceptible adult populations exist.
3. Int J Gynaecol Obstet 1993 Aug;42(2):189-98 Hepatitis in pregnancy. ACOG Technical Bulletin Number 174--November 1992. : Serious complications of hep A are uncommon
4. Int J Gynaecol Obstet 1998 Nov;63(2):195-202 ACOG educational bulletin. Viral hepatitis in pregnancy. Number 248, July 1998 (replaces No. 174, November 1992). American College of Obstetricians and Gynecologists. Hepatitis A is an uncommon complication of pregnancy and is not associated with perinatal transmission. In contrast, hepatitis B virus infection is more common and clearly poses a serious risk to the household contacts and neonates of infected mothers. Accordingly, all pregnant women should be tested for hepatitis B virus. Universal vaccination of all neonates with hepatitis B vaccine is now recommended. Infants delivered to HBsAg seropositive mothers also should receive HBIG and vaccination immediately after birth. Hepatitis E is extremely rare in the United States and is quite similar to hepatitis A, although perinatal transmission does occur with hepatitis E. Hepatitis C and D, which are transmitted parenterally and by sexual contact, have been associated with vertical transmission. No immunoprophylaxis currently is available for neonates of mothers with hepatitis C or E virus. Immunization against hepatitis B is protective against vertical transmission of hepatitis D.
5. Dinsmoor MJ. Hepatitis in the obstetric patient. Infect Dis Clin North Am 1997 Mar;11(1):77-91 The six agents identified thus far that cause viral hepatitis are reviewed, and their impact upon pregnancy is described. Although it is the most common cause of jaundice during pregnancy, viral hepatitis does not generally increase the risk of pregnancy complications, nor is it teratogenic. Vertical transmission of some types of viral hepatitis does occur, however. Acute hepatitis A in pregnancy does not appear to carry a different prognosis than in the nonpregnant, nor is there any evidence that the pregnant patient is more susceptible
6. Steffen R. Hepatitis A and hepatitis B: risks compared with other vaccine preventable diseases and immunizations recommended. Vaccine 1993;11:518–520. Rates as high as 20 per 1,000 are seen in overland travelers living and eating under poor hygienic conditions. Hepatitis A is usually no more severe during pregnancy than at other times and does not affect the outcome of pregnancy. There have been reports, however, of acute fulminant disease in pregnant women during the third trimester when there is also an increased risk of premature labor and fetal death
7. Gilbert GL. Miscellaneous viral infections. In: Infectious diseases in pregnancy and the newborn infant. Chur, Switzerland: Harwood Academic, 1991
8. Jaiswal SP, Jain AK, Naik G, Soni N, Chitnis DS.. Viral hepatitis during pregnancy. Int J Gynaecol Obstet 2001 Feb;72(2):103-108. OBJECTIVE: A great degree of controversy prevails over the existing reports on the severity and outcome of acute viral hepatitis (AVH) during pregnancy. The present study describes the outcome of AVH associated with pregnancy. A correlation was also assessed for gestation period, viral etiology and outcome of AVH. METHOD: The serum samples of 273 females with viral hepatitis (age group 18--23 years) were included in the study. Among them, 127 females were pregnant and 146 were non-pregnant cases (as a control group). The sera were screened for seromarkers of the hepatitis A virus (HAV) through to the hepatitis E virus (HEV) by the latest available generation ELISA kits. Among the 127 pregnant females, 83 were AVH cases, while 44 were fulminant hepatic failure (FHF) cases. Among the 146 non-pregnant females, 129 were AVH and 17 were FHF cases. RESULT: Among the AVH pregnant females, 73 (57.5%) had HEV infection. Fifty-eight percent of the HEV infected pregnant females were associated with FHF. Among non-pregnant females HEV was documented in 67 (46%) cases. HBV infection was observed in 19% and 18% of the pregnant and non-pregnant females, respectively. Twenty percent of the pregnant and 33% of the non-pregnant females remained non-reactive for seromarkers of HAV-HEV. The mortality rate was highest (56%) among HEV infected FHF cases during third trimester of pregnancy. The chi(2) test was applied to check the statistical significance for the differences over the prevalence in various groups. CONCLUSION: In the present study, HEV was found to be the chief etiological agent, associated with higher morbidity and mortality. However, the incidence of HEV in pregnant females was not significantly different from non-pregnant females. The prevalence of HAV, HCV and HDV were very low in the study. An increased incidence of FHF was noted among HEV infected pregnant females, while infection with an agent other than A-E was commonly associated with FHF among non-pregnant females.
9. Menendez C, Sanchez-Tapias JM, Kahigwa E, Mshinda H, Costa J, Vidal J, Acosta Smith JL.. Foodborne infections during pregnancy.. J Food Prot 1999 Jul;62(7):818-829. 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
10. Michielsen PP, Van Damme P. Viral hepatitis and pregnancy. Acta Gastroenterol Belg 1999 Jan;62(1):21-29. This paper reviews data on the mutual relationship between pregnancy and viral hepatitis and the mother-to-infant transmission of the virus. In the western world, hepatitis A, B or C do not seem to influence the course of pregnancy, or to be associated with foetal risks. In contrast, women who contract a hepatitis E infection in their third trimester of pregnancy have a relatively high probability to develop a fulminant hepatitis. Mother-to-infant transmission of hepatitis A seems to be very uncommon. On the contrary, HBsAg and HBeAg positive mothers have a 80-90% risk to transmit the disease to their offspring, more than 85% of these becoming chronic carriers of HBsAg. The risk depends on the level of viral replication. In HBsAg positive and HBeAg negative mothers the rate of transmission is only 2-15%, these babies rarely become carriers. A possible explanation is the transplacental passage of the HBeAg making the infant tolerant to the hepatitis B virus. As most of the infections occur during or directly after delivery, the neonates are suitable for postexposure prophylaxis. It is recommended by the Centers for Disease Control and Prevention and the American Academy of Pediatrics that newborns of HBsAg positive mothers should receive hepatitis B immunoglobulins within 12 hours after birth concurrently with the first paediatric dose of the vaccine. Vaccination should be completed at 1 and 6 months. This regimen confers a protective efficacy of > or = 90%. Vertical transmission of hepatitis C is considered to be relatively rare, around 11% when HCV-RNA is positive. The highest rates of vertical transmission of HCV are noted in women with high HCV-RNA level or concurrent HIV infection. The risk is extremely low when no HCV-RNA is detected. There is currently no treatment to prevent this vertical transmission; routine screening of all mothers is unwarranted, and pregnancies among HCV-positive mothers should not be discouraged, but their infants should be tested for anti-HCV at 1 year and followed for the development of hepatitis. Breast feeding does not seem to play an important role in the transmission of hepatitis B and C.
11. Hunt CM, Sharara AI. Liver disease in pregnancy. Am Fam Physician 1999 Feb 15;59(4):829-836. Acute viral hepatitis is the most common cause of jaundice in pregnancy. The course of acute hepatitis is unaffected by pregnancy, except in patients with hepatitis E and disseminated herpes simplex infections, in which maternal and fetal mortality rates are significantly increased. Chronic hepatitis B or C infections may be transmitted to neonates; however, hepatitis B virus transmission is effectively prevented with perinatal hepatitis B vaccination and prophylaxis with hepatitis B immune globulin. Cholelithiasis occurs in 6 percent of pregnancies; complications can safely be treated with surgery. Women with chronic liver disease or cirrhosis exhibit a higher risk of fetal loss during pregnancy. Preeclampsia is associated with HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome, acute fatty liver of pregnancy, and hepatic infarction and rupture. These rare diseases result in increased maternal and fetal mortality. Treatment involves prompt delivery, whereupon the liver disease quickly reverses. Therapy with penicillamine, trientine, prednisone or azathioprine can be safely continued during pregnancy.
12. Duff P. Hepatitis in pregnancy. Semin Perinatol 1998 Aug;22(4):277-283. Currently, six distinct types of hepatitis virus have been identified: A, B, C, D, E, and G. Hepatitis A virus infection does not cause a chronic carrier state, and perinatal transmission is extremely uncommon. Hepatitis B can be transmitted perinatally, but immunization of the newborn with hepatitis B immune globulin and hepatitis B vaccine markedly reduces the risk of neonatal infection. Hepatitis D virus is dependent on coinfection with the hepatitis B virus for replication. Immunoprophylaxis against hepatitis B also is effective against hepatitis D. Hepatitis C virus is primarily transmitted by the parenteral route and is particularly likely to cause chronic liver disease. Perinatal transmission of hepatitis C principally occurs in women who have high titers of HCV-RNA or who are coinfected with human immunodeficiency virus. At this time, no immunoprophylaxis for hepatitis C is available. Hepatitis G, a recently described organism, is related to hepatitis C. Its clinical significance remains undetermined. Hepatitis E is transmitted in a manner similar to hepatitis A. Perinatal transmission is unusual, but maternal disease is often severe.
13. Magriples U. Hepatitis in pregnancy. Semin Perinatol 1998 Apr;22(2):112-117. The study of viral hepatitis was expanded over the past decade with the emergence of new viruses, therapies, and vaccination guidelines as well as new data on the risks of perinatal transmission. There are now at least six hepatitis viruses. Hepatitis A and E are causes of epidemic, enteric infection and do not carry a significant risk of chronic infection. Hepatitis B, C, D, and G are hematogenously spread and are significant causes of chronic hepatitis, hepatocellular carcinoma, and cirrhosis. The following report reviews the types of hepatitis as well as the consequences of infection to the mother and fetus.
14. Yang H, Li Z, Qi W. [Clinical analysis of 39 cases of hepatitis E in pregnancy]. Zhonghua Fu Chan Ke Za Zhi 1997 Feb;32(2):78-80 [Article in Chinese]. OBJECTIVE: To introduce clinical manifestations and treatment of hepatitis E in pregnancy. METHODS: Thirty-nine cases of hepatitis E in pregnancy, were analysed from June. 1992 to Jun. 1994, retrospectively on its epidemiologic characteristics, clinical manifestations and prognosis. RESULTS: The prognosis of sporadic cases of hepatitis E in pregnancy was good and its main complications were premature rupture of membranes, uterine inertia and fetal distress. CONCLUSIONS: Sporadic case is the main form of hepatitis E in pregnancy in Beijing. Active treatment and intensive monitoring would improve its prognosis.
15. Hussaini SH, Skidmore SJ, Richardson P, Sherratt LM, Cooper BT, O'Grady JG. Severe hepatitis E infection during pregnancy. J Viral Hepat 1997 Jan;4(1):51-54. In areas with endemic hepatitis E virus (HEV), acute liver failure secondary to hepatitis E infection is common in pregnancy and associated with a mortality rate of up to 20%. However, there is little information on the clinical course of severe hepatitis E infection during pregnancy in non-endemic areas such as the UK. Here we describe two cases of severe hepatitis E in pregnancy in patients returning from the Indian subcontinent. These cases were diagnosed by the detection of IgM anti-HEV antibody using an enzyme immunoassay with recombinant hepatitis E viral antigens. The first case describes acute hepatic failure, with coagulopathy and encephalopathy, warranting intensive therapy and elective ventilation. In the other case, the patient had severe hepatitis with coagulopathy. Both cases spontaneously resolved with no foetal loss. These cases highlight the need for suspicion of HEV infection in patients returning from endemic areas and presenting with acute non-A non-B hepatitis, especially when pregnant. Furthermore, the intensive treatment of acute liver failure caused by HEV may reduce the high mortality reported in Asia.
16. Mast EE, Purdy MA, Krawczynski K. Hepatitis E. Baillieres Clin Gastroenterol 1996 Jul;10(2):227-242. Hepatitis E has a world-wide distribution and causes substantial morbidity and mortality in some developing countries, particularly among pregnant women. Hepatitis E virus (HEV) has recently been cloned and sequenced, and new diagnostic tests have been developed. These tests have been used to begin to characterize the natural history and epidemiological features of HEV infection. Experimental vaccines have also been developed that offer the potential to prevent hepatitis E. However, much remains to be learned about HEV, including the mechanisms of transmission, the reservoir(s) of the virus, and the natural history of protective immunity in order to develop effective strategies to prevent this disease.
17. Hamid SS, Jafri SM, Khan H, Shah H, Abbas Z, Fields H. Fulminant hepatic failure in pregnant women: acute fatty liver or acute viral hepatitis? J Hepatol 1996 Jul;25(1):20-27. BACKGROUND: Hepatitis E virus, which is endemic in our region, can cause severe liver dysfunction in pregnant women and this can be clinically confused with acute fatty liver of pregnancy. METHODS: We studied the clinical and laboratory data as well as the maternal and fetal outcomes of 12 pregnant women presenting with fulminant hepatic failure in order to determine the etiology of the disease. The clinical diagnoses were subsequently correlated with serologic assays for acute HEV infection. All patients were severely ill with deep jaundice, grade 3-4 encephalopathy and abnormal prothrombin times. RESULTS: A clinical diagnosis of acute viral hepatitis was made in nine patients and of acute fatty liver in the other three cases. IgM and IgG antibodies confirmed acute viral hepatitis E in six of the nine patients while one had acute hepatitis A infection. HEV IgM and IgG antibodies were, however, also positive in two of the three patients thought to have acute fatty liver. Maternal and fetal mortality were 16.6% and 50%, respectively. CONCLUSIONS: We conclude that hepatitis E is the usual cause of acute liver failure in our pregnant women and that clinical and laboratory features do not permit accurate distinction between acute HEV infection and acute fatty liver of pregnancy. The prognosis in patients with acute HEV infection is much better than in other groups with severe liver failure (mortality 16% vs 68%).
18. Khuroo MS, Kamili S, Jameel S. Vertical transmission of hepatitis E virus. Lancet 1995 Apr 22;345(8956):1025-1026. Little is known about vertical transmission of hepatitis E virus from infected mothers to their infants. We studied eight babies born to mothers infected with hepatitis E in third trimester. One baby was icteric at birth with elevated transaminases and four babies had anicteric hepatitis. Two babies were born with hypothermia and hypoglycaemia and died within 24 h; one had massive hepatic necrosis. Hepatitis E virus RNA was detected by PCR in cord or birth blood samples of five infants. Six infants had evidence of hepatitis E infection. We conclude that hepatitis E virus is commonly transmitted from infected mothers to their babies with significant perinatal morbidity and mortality.
19. Figueroa Damian R, Villagrana Zesati R, Sanchez Fernandez L, Benavides Covarrubias E. [Course of pregnancies complicated by viral hepatitis]. Ginecol Obstet Mex 1994 Aug;62:243-248 [Article in Spanish]. It has been described that viral hepatitis is the most frequent cause of jaundice in the pregnant women. In this article we present clinical cases of hepatitis in pregnancy and review the new knowledge about the perinatal repercussion of this association. Hepatitis A is rare in pregnant women and has not a significant perinatal risk. Hepatitis B virus (HBV) can be transmitted from mother to child by transplacental way or at born. Between 40 to 80 per cent of the children infected by this route will develop chronic hepatitis, so the infants of HBsAg carrier mothers must be immunized at birth. The perinatal transmission of hepatitis C virus has been proved but the repercussion in the fetus or newborn is unknown. Hepatitis D virus can only be transmitted from mother to child together with HBV. Hepatitis E has been associated with a mortality from 10 to 40 per cent in pregnant women and with an increase in the preterm pregnancy.
20. Reinus JF, Leikin EL. Viral hepatitis in pregnancy. Clinics in Liver Disease, Volume 3 • Number 1 • February 1999
21. Riely CA. Hepatic disease in pregnancy. Am J Med 1994 Jan 17;96(1A):18S-22S. Liver disease occurring in pregnancy can be categorized into three groups. The first group includes diseases unique to pregnancy and caused by it. Among these are hyperemesis gravidarum, cholestasis of pregnancy, and disorders associated with preeclampsia. Liver involvement may be expected in 50% of patients with hyperemesis gravidarum. Preeclampsia has been associated with both the HELLP syndrome (hemolysis, elevated liver tests, and low platelets), which includes hepatic infarction and rupture, and with acute fatty liver of pregnancy (AFLP). In patients with HELLP syndrome, liver test abnormalities do not correlate with liver injury. Therefore, this and other disorders associated with preeclampsia require aggressive treatment, primarily with delivery. The second group of liver diseases are those exacerbated by pregnancy. Viral infections involving the liver that are usually benign, such as hepatitis E and herpes simplex, are more likely to be exacerbated in pregnant women and are more likely to lead to fulminant hepatic failure. Cholelithiasis and Budd-Chiari syndrome are more prevalent in pregnant women. The third group is comprised of liver diseases that are preexisting in the pregnant patient and includes autoimmune chronic active hepatitis and Wilson's disease. The number of patients in the last group is small, as chronic liver disease is rare in women who are able to bear children.
HIV
1. Leroy V, Dabis F. [Reduction of mother-child transmission of HIV infection in Africa: from clinical research to public health programs]. Med Trop (Mars) 1999;59(4 Pt 2):456-464. [Article in French]. More and more African women are infected by HIV. As a result the mother-to-child transmission (MCT) rate is rising. Various prevention techniques have been assessed in randomized clinical trials in Africa but results need to be discussed to understand the full implications for prevention programs. To gain insight into this issue, we reviewed 11 randomized trials conducted in Africa and several other studies from developed countries. Trials using antiretroviral (ARV) drugs demonstrated good results for prevention of MCT in the first six months of life using abbreviated regimens involving either zidovudine (with or without lamivudine) or nevirapine alone. Preliminary results suggest long-term effectiveness of zidovudine. Antiseptic and nutritional interventions have demonstrated some efficacy in reducing maternal and newborn morbidity and mortality but have no effect on MCT rate. Confidential, voluntary HIV screening and counseling of pregnant women and short-course ARV treatment during the perinatal period associated with alternatives to breast-feeding such as early weaning or replacement of breast milk at birth are now the best methods to reduce MCT. Prevention of postnatal transmission will require further study in particular with regard to effects of different methods of feeding and post-exposure prophylaxis using ARV drugs in newborns. Management of HIV-infected children must remain a high priority. Implementation of currently available strategies is now under discussion.
2. Kass NE, Taylor HA, Anderson J. Treatment of human immunodeficiency virus during pregnancy: The shift from an exclusive focus on fetal protection to a more balanced approach. American Journal of Obstetrics and Gynecology, Volume 182 • Number 4 • April 2000. A review is presented of policy and treatment guidelines for human immunodeficiency virus infection in pregnancy. Interventions that serve the best interests of pregnant women and their fetuses are suggested. Reproductive studies with animals should be done routinely, and more research with pregnant women should be conducted. Women and their health care providers need to shift away from the "therapeutic nihilism" paradigm. All clinical decisions must be made cautiously and thoughtfully, with the understanding that the health needs of the pregnant woman are usually whatever is in the best interest of the developing fetus.
3. Krist AH. Obstetric Care in Patients with HIV Disease. American Family Physician, Volume 63 • Number 1 • January 1, 2001. Appropriate management of pregnant patients who have human immunodeficiency virus (HIV) disease can have a major impact on maternal and infant health. The goals of therapy are to properly manage the pregnancy, treat the maternal HIV infection and minimize the risk of vertical transmission of HIV. Early detection of HIV through aggressive screening programs is necessary to initiate timely therapy. Zidovudine therapy given antepartum and intrapartum to the mother and after birth to the newborn has been shown to decrease the risk of vertical transmission. Evidence suggests that more aggressive antiretroviral therapy for the mother, which allows suppression of viral loads to undetectable levels, may be safe and may provide significant additional benefits. However, treatment needs to be individualized, weighing the possible teratogenic risks against the benefits of decreased transmission. Multiple prospective cohort studies support elective cesarean section as an additional means to decrease vertical transmission, but its role in relation to other therapies has not been determined. As in nonpregnant patients infected with HIV, prevention of opportunistic infections and adequate psychosocial support are essential.
4. Brettle RP. Pregnancy and its effect on HIV/AIDS. Clin Obstet Gynecol 1992;6:125-36.
5. Meda N, Leroy V, Viho I, Msellati P, Yaro S, Mandelbrot L, Montcho C, Manigart O, Dabis F; Field acceptability and effectiveness of the routine utilization of zidovudine to reduce mother-to-child transmission of HIV-1 in West Africa. AIDS 2002 Nov 22;16(17):2323-8. OBJECTIVE: To ascertain the field acceptability and effectiveness of the routine utilization of zidovudine in reducing mother-to-child transmission (MTCT) of HIV in breastfed children after a randomized clinical trial demonstrated its efficacy in Cote d'Ivoire and Burkina Faso. METHODS: Pregnant women aged 18 years or older, who had confirmed HIV-1 infection, haemoglobinemia greater than 7 g/dl were enrolled in an open label cohort at 36-38 weeks' gestation to receive an oral short course of zidovudine. Paediatric HIV infection was defined as a positive HIV-1 polymerase chain reaction, or if aged 15 months or older, a positive HIV serology. RESULTS: The acceptability of HIV pretest counselling was significantly higher in the cohort (90.3%) than in the trial (83.7%) (P < 0.001), but the return rate for HIV test results and for inclusion was low. A similar proportion of women accepted starting zidovudine in the cohort, 30.4% compared with 27.3% in the trial (P = 0.13). The proportions of women who took more than 80% of the expected zidovudine regimen were 81.8% before labour, 86.7% during labour, and 88.1% during the postpartum period, compared with those observed during the trial, 78.1, 81.1, and 85%, respectively. The MTCT probability at age 15 months was 19.6% in the cohort (n = 185) versus 21.2% in the trial (P = 0.52). CONCLUSION: The major drawback with the implementation of a short zidovudine regimen to reduce MTCT is HIV counselling and testing procedures. For women who consent, zidovudine is well accepted and efficacious under routine circumstances. Copyright 2002 Lippincott Williams & Wilkins
West Nile Virus
1. Centers for Disease Control and Prevention (CDC) Interim guidelines for the evaluation of infants born to mothers infected with West Nile virus during pregnancy. MMWR Morb Mortal Wkly Rep. 2004 Feb 27;53(7):154-7. West Nile virus (WNV) is a single-stranded RNA flavivirus with antigenic similarities to Japanese encephalitis and St. Louis encephalitis viruses. It is transmitted to humans primarily through the bites of infected mosquitoes. Flavivirus infection during pregnancy has been associated rarely with both spontaneous abortion and neonatal illness but has not been known to cause birth defects in humans. During 2002, a total of 4,156 cases of WNV illness in humans, including 2,946 cases of neuroinvasive disease, were reported to CDC by state health departments. In 2002, a woman who had WNV encephalitis during the 27th week of her pregnancy delivered a full-term infant with chorioretinitis, cystic destruction of cerebral tissue, and laboratory evidence of congenitally acquired WNV infection. Although this case demonstrated intrauterine WNV infection in an infant with congenital abnormalities, it did not prove a causal relation between WNV infection and these abnormalities. During 2002, CDC investigated three other instances of maternal WNV infection. In all three cases, the infants were born at full term with normal appearance and negative laboratory tests for WNV infection; cranial imaging studies and ophthalmologic examinations were not performed. During 2003, CDC received reports of approximately 9,100 cases of WNV illness, including approximately 2,600 cases of neuroinvasive disease. CDC is gathering data on pregnancy outcomes for approximately 70 women with WNV illness during pregnancy.
2. O'Leary DR, Kuhn S, Kniss KL, et al. Birth outcomes following West Nile Virus infection of pregnant women in the United States: 2003-2004. Pediatrics. 2006 Mar;117(3):e537-45. CONCLUSIONS: Of 72 infants followed to date in 2003 and 2004, almost all seemed normal, and none had conclusive laboratory evidence of congenital WNV infection. Three infants had WNV infection that could have been congenitally acquired. Seven infants had major malformations, but only 3 of these had defects that could have been caused by maternal WNV infection based on the timing of the infections and the sensitive developmental period for the specific malformations, and none had any conclusive evidence of WNV etiology. However, the sensitivity and specificity of IgM testing of cord blood to detect congenital WNV infection are currently unknown, and congenital WNV infection among newborns with IgM-negative serology cannot be ruled out.
Dengue fever
1. Carles, G., A. Talarmin, C. Peneau, and M. Bertsch. 2000. [Dengue fever and pregnancy. A study of 38 cases in french Guiana]. J Gynecol.Obstet.Biol.Reprod.(Paris) 29, no. 8:758-762. CONCLUSION: In case of dengue fever infection of the mother during pregnancy, there is a serious risk of premature birth and fetal death. In case of infection close to term, there is a risk of hemorrhage for both the mother and the newborn
2. Sirinavin, S., P. Nuntnarumit, S. Supapannachart, S. Boonkasidecha, C. Techasaensiri, and S. Yoksarn. 2004. Vertical dengue infection: case reports and review. Pediatr.Infect.Dis.J 23, no. 11:1042-1047. Abstract: Two vertical dengue infection cases are presented, and 15 others are reviewed. Twelve mothers had fever 0-9 (median, 2) days antepartum. The fevers of 17 neonates occurred at 1-11 (median, 4) days of life and lasted for 1-5 (median, 3) days. Neonatal thrombocytopenia was detected at 1-11 (median, 6) days of life and lasted for 3-18 (median, 6) days; the lowest platelet counts were 5-75 x 10(3) (median, 19 x 10 (3))/mm3. One neonate died.
3. Perret, C., P. Chanthavanich, K. Pengsaa, K. Limkittikul, J. E. G. Bunn, B. J. Brabin, and P. Hutajaroen. 2005. Dengue infection during pregnancy and transplacental antibody transfer in Thai mothers. Journal of Infection 51, no. 4:287-293. OBJECTIVES: The objectives of this study were to estimate dengue seroprevalence in a population of Thai pregnant women, living in a highly endemic area and placental transfer of dengue antibodies. METHODS: A cross-sectional seroprevalence study of 245 pregnant women at delivery. RESULTS: Dengue HAI antibodies were positive in 94.7%. Maternal age was the only risk factor associated with dengue infection as older mothers (>20 years) were significantly more likely to be seropositive than younger women (p<0.0001). Cord antibody titres varied with maternal age and antibody titre, were significantly higher in babies born to younger mothers (<20 years) (p=0.01), and were significantly correlated with maternal titre. Low birthweight babies had lower transfer ratios for DEN-2 antibody (1.06) compared to heavier babies (1.36, p=0.05). No mother or neonate had dengue IgM detected. Two women were classified as recently, but not currently infected with dengue virus and we consider it likely these were first trimester infections. As no infant became infected the fetal infection was 0%. CONCLUSIONS: Younger mothers were more likely to have been recently infected, resulting in higher antibody titres. Maternal dengue antibody transfer was proportional to maternal antibody concentration. |