Sexual Dysfunction in Premenopausal Women Treated for Breast Cancer - Implications for their Clinical Care.

Breast cancer is the commonest cancer in women globally. Early stage diagnosis in young sexually active women, coupled with advances in adjuvant therapy has contributed to an increase in the number of young survivors. A diagnosis of breast cancer may affect the woman's self-esteem, sexuality and intimate relationships. Surgical alteration or loss of the breast, a symbol of femininity and sexuality, may negatively impact her body-image. Chemotherapy may cause ovarian damage leading to premature menopause. The psychological effects thereof may impair the man's ability to offer emotional support to the woman as well as affect their relationship. These may affect a survivor's sexual functioning and quality of life. This paper reports on four pre-menopausal women treated for breast cancer and the sexual sequels thereof. It is aimed at raising awareness amongst health providers managing women with breast cancer in sub-Saharan Africa on the impact thereof of their quality of life as well as sexual functioning. Treatment of breast cancer has focused mainly on improved survival with no due consideration of its impact on quality of life. There is need for multi-disciplinary approach in managing these patients to address all concerns in a wholesome manner.

Urinary Tract Infection In Young Healthy Women Following Heterosexual Anal Intercourse: Case Reports.

Urinary tract infections (UTIs) are among the most common bacterial infections in outpatient clinical settings globally. Young healthy women are at highest risk of community-acquired UTI. While uncomplicated UTI is not life-threatening, it is associated with high morbidity and treatment costs. The pathogenesis of urinary tract infection in young healthy women is complex. It is influenced by a number of host biological and behavioural factors and virulence of the uropathogen. The infecting uropathogens in community-acquired UTI originate from the fecal flora, E. coli being the most predominant, accounting for 80-90% of these UTIs. Vaginal colonization with uropathogens, a pre-requisite for bladder infection may be facilitated by sexual intercourse, which has been shown to be a strong risk factor and predictor of UTI. While majority of studies have explored the association between heterosexual vaginal intercourse and UTI in healthy young women, the possible association with heterosexual receptive anal intercourse has not received adequate attention despite evidence of high prevalence globally. This paper presents two young healthy married women who had severe UTI following heterosexual anal intercourse and discusses possible association thereof. Understanding the risk factors for UTI and identification of possible predisposing conditions in a particular individual are important in guiding therapeutic approaches and preventive strategies. Cognisant of reportedly high prevalence of various sexual practices including receptive heterosexual anal intercourse and their impact on individuals' health, details on sexual history should always be enquired into in young women presenting with genito-urinary complaints.

Unconsummated marriage in sub-Saharan Africa: case reports.

Unconsummated marriage is a condition where newly married couples are unable to achieve penile-vaginal intercourse for variable periods despite desire and several attempts to do so. Its exact cause(s) is/are unknown, but performance anxiety resulting from or leading to other conditions is reportedly the major etiological factor. It is thought to be more prevalent in traditional and conservative religious communities where premarital sexual exposure is strictly prohibited. Most publications on unconsummated marriage have originated from North America, European and Middle Eastern countries. There have not been any such reports from sub-Saharan Africa, which is home to diverse cultures and traditions regarding premarital sex and marriage. This paper presents a sample of four cases with unconsummated marriage managed by the author in his private clinic based in the city of Nairobi Kenya, over the past five years. Possible etiological factors and management approaches are discussed, with a review of relevant literature.

Sexual dysfunction among HIV patients: three case reports and review of literature.

Global efforts in addressing the HIV/AIDS epidemic have focused on preventing new infections, reduction of viral loads through treatment and care and support for the patients. Hardly any attention has been given to their quality of life in particular sexual health and functioning. There is a growing body of literature indicating high prevalence of sexual problems amongst HIV-infected individuals, whose mechanisms remain unclear. This may affect individuals' quality of life, interpersonal relationships and HIV treatment. The sub-Saharan Africa (SSA) region is the epicentre of the HIV epidemic, majority of the patients being young (< 30 years old) and in long-term heterosexual relationships. With increased life expectancy due to expanded access to HAART, the prevalence and potential impact of sexual dysfunction are certain to be significant. There is urgent need for appropriate research on sexual experiences and functioning amongst HIV patients in SSA and appropriate interventions to address them. Current efforts to link HIV/AIDS and sexual and reproductive health and rights (SRHR) and proposals to make SRH services integrated and comprehensive provide are a good starting point. However SRHR policies, strategic plans and programmes should be reviewed to ensure inclusion of sexual health.

Prevalence of and factors associated with female sexual dysfunction among women using hormonal and non-hormonal contraception at the AGA Khan University Hospital Nairobi.

BACKGROUND: Female sexual function (FSD) is a complex phenomenon. It integrates all body systems and is influenced by a variety of factors. Contraceptives have shown to have variable effects on FSD. In Kenya, the majority of women use hormonal contraception with high rates of discontinuation of use, attributed to related side effects such as weight loss and loss of libido. AIM: To determine the prevalence of and the factors affecting FSD among women using contraception in our setting. SETTING: The study was carried out at the Aga Khan University Hospital, Nairobi, at various clinical sites. METHODS: A cross-sectional study was conducted. Consecutive sampling of women of reproductive age using either hormonal or non-hormonal contraception was conducted. Two questionnaires were completed after obtaining informed consent. Independent associations of factors with the outcome variables were assessed using the chi-square test of association, and variables with a p 0.25 were used in the multivariate analysis. Factors associated with FSD were determined using binary logistic regression. RESULTS: A total of 566 participants were included. The prevalence of FSD among those using hormonal and those using non-hormonal contraception was 51.5% and 29.6%, respectively (p 0.0001). We found that the factors associated with FSD were presence of chronic illness and use of chronic medication, being self-employed or unemployed, alcohol intake and history of miscarriage(s). CONCLUSION: There was a high prevalence of and a strong association between hormonal contraception and FSD. More studies on this topic in different settings are recommended to investigate the effect of each type of hormonal method on FSD.

Association of Female Sexual Dysfunction and Fertility: a cross sectional study.

BACKGROUND: Sexual function plays an essential role in the bio-psychosocial wellbeing and quality of life of women and disturbances in sexual functioning often result in significant distress. Female sexual dysfunction (FSD) and subfertility are common problems affecting approximately 43 and 20% of women respectively. However, despite the high prevalence of both conditions, little has been studied on the effects of subfertility on sexual functioning especially in sub-Saharan Africa. We set out to compare the prevalence of female sexual dysfunction in patients on assessment for sub-fertility and those either seeking or already on fertility control services at a private tertiary teaching hospital in Kenya. METHODS: This was an analytical cross sectional study. Eligible women of reproductive age (18-49 years), attending the gynaecological clinics with complaints of subfertility and those seeking fertility control services were requested to fill a general demographic tool containing personal data and the Female Sexual Function Index (FSFI) questionnaire after informed consent. Prevalence of sexual dysfunction was calculated as a percentage of patients not achieving an overall FSFI score of 26.55. Univariate and multivariate analysis were done to compare clinical variables to delineate the potential association. RESULTS: The prevalence of female sexual dysfunction was 31.2% in the subfertile group and 22.6% in fertility control group. The difference was not statistically significant (p = 0.187). The mean domain and overall female sexual function scores were lower in the subfertile group than the fertility control group though this was not statistically significant. The most prevalent sexual domain dysfunctions in both the subfertility and fertility control groups were desire and arousal while the least in both groups was satisfaction dysfunction. Subfertility type was not associated with sexual dysfunction. Higher education attainment was protective of female sexual dysfunction in the subfertile group while use of hormonal contraception was associated with greater sexual impairment in the fertility control group. On logistic regression analysis, higher maternal age and alcohol use appeared to be protective against sexual dysfunction. CONCLUSION: The present study demonstrated no association between the fertility status and the prevalence female sexual dysfunction. Subfertility type was not associated with sexual dysfunction. Education level and hormonal contraception use were associated with female sexual dysfunction in the subfertile and fertility control groups respectively while alcohol use and higher maternal age appeared to be protective against sexual dysfunction.

Short postexposure prophylaxis in newborn babies to reduce mother-to-child transmission of HIV-1: NVAZ randomised clinical trial.

BACKGROUND: In sub-Saharan Africa, most women present late for delivery with unknown HIV status, which limits the use of intrapartum nevirapine to prevent mother-to-child transmission of HIV. We aimed to determine whether post-exposure prophylaxis of nevirapine plus zidovudine given to babies only reduced transmission of HIV more than did a regimen of nevirapine alone. METHODS: We randomly assigned 1119 babies of Malawian women with HIV-1 who presented late (ie, within 2 h of expected delivery) to either nevirapine alone or nevirapine and zidovudine. Both drugs were given immediately after birth: one dose of nevirapine (2 mg/kg weight) was given as a single dose; babies in the nevirapine plus zidovudine group also received zidovudine twice daily for 1 week (4 mg/kg weight). Infant HIV infection was determined at birth and at 6-8 weeks. Primary outcome was HIV infection in babies at 6-8 weeks in those not infected at birth. Analysis was by intention to treat. FINDINGS: The overall rate of mother-to-child transmission at 6-8 weeks was 15.3% in 484 babies who received nevirapine and zidovudine and 20.9% in 468 babies who received nevirapine only (p=0.03). At 6-8 weeks, in babies who were HIV negative at birth, 34 (7.7%) babies who had nevirapine and zidovudine and 51 (12.1%) who received nevirapine only were infected (p=0.03)-a protective efficacy of 36%. This finding remained after controlling for maternal viral load and other factors at baseline. Adverse events were mild and of similar frequency in the two groups. INTERPRETATION: Postexposure prophylaxis can offer protection against HIV infection to babies of women who missed opportunities to be counselled and tested before or during pregnancy. The nevirapine and zidovudine regimen is safe and easy to implement.

Impairment of humoral immunity to Plasmodium falciparum malaria in pregnancy by HIV infection.

BACKGROUND: HIV infection increases the risk of malaria infection in pregnant women. Antibodies to variant surface antigens (VSA) on infected erythrocytes might protect against malaria in pregnancy. We postulated that HIV-induced impairment of humoral immunity to VSA mediates the increased susceptibility to malaria. METHODS: We compared serum concentrations of antibodies to VSA by flow cytometry or agglutination, and to merozoite proteins AMA-1 and MSP119 by ELISA, in 298 pregnant Malawian women, and related the findings to malaria and HIV infection, CD4-positive T-cell count, and HIV-1 viral load. FINDINGS: Concentrations of IgG to placental type VSA were lower in HIV-infected women than in HIV-uninfected women (median 8 units [IQR 4-23] vs 20 [12-30]; p<0.0001), among women with malaria (p=0.009) and those without malaria (p=0.0062). The impairment was greatest in first pregnancy. Agglutinating antibodies to placental VSA were present in a lower proportion of HIV-infected than HIV-uninfected women (58 [35.1%] of 165 vs 50 [53.8%] of 93, p<0.001). The degree of antibody binding by flow cytometry was correlated with CD4-positive T-cell count (r=0.16, p=0.019) and inversely with HIV-1 viral load (r=-0.16, p=0.030). Concentrations of antibodies to AMA-1 were lower in HIV infection (p<0.0001) but were not correlated with CD4-positive T-cell count or viral load. Responses to MSP119 were little affected by HIV infection. In multivariate analyses, HIV was negatively associated with amount of antibody to both VSA and AMA-1 (p<0.001 for each) but not MSP119. INTERPRETATION: HIV infection impairs antimalarial immunity, especially responses to placental type VSA. The impairment is greatest in the most immunosuppressed women and could explain the increased susceptibility to malaria seen in pregnant women with HIV infection.

Malaria during pregnancy and foetal haematological status in Blantyre, Malawi.

BACKGROUND: Although maternal anaemia often stems from malaria infection during pregnancy, its effects on foetal haemoglobin levels are not straightforward. Lower-than-expected cord haemoglobin values in malarious versus non-malarious regions were noted by one review, which hypothesized they resulted from foetal immune activation to maternal malaria. This study addressed this idea by examining cord haemoglobin levels in relation to maternal malaria, anaemia, and markers of foetal immune activation. METHODS: Cord haemoglobin levels were examined in 32 malaria-infected and 58 uninfected women in Blantyre, Malawi, in relation to maternal haemoglobin levels, malaria status, and markers of foetal haematological status, hypoxia, and inflammation, including TNF-alpha, TGF-beta, and ferritin. All women were HIV-negative. RESULTS: Although malaria was associated with a reduction in maternal haemoglobin (10.8 g/dL vs. 12.1 g/dL, p < 0.001), no reduction in cord haemoglobin and no significant relationship between maternal and cord haemoglobin levels were found. Cord blood markers of haematological and hypoxic statuses did not differ between malaria-infected and uninfected women. Maternal malaria was associated with decreased TGF-beta and increased cord ferritin, the latter of which was positively correlated with parasitaemia (r = 0.474, p = 0.009). Increased cord ferritin was associated with significantly decreased birth weight and gestational length, although maternal and cord haemoglobin levels and malaria status had no effect on birth outcome. CONCLUSION: In this population, cord haemoglobin levels were protected from the effect of maternal malaria. However, decreased TGF-beta and elevated ferritin levels in cord blood suggest foetal immune activation to maternal malaria, which may help explain poor birth outcomes.

Status of carotenoids, vitamin A, and vitamin E in the mother-infant dyad and anthropometric status of infants in Malawi.

This prospective study was carried out during February 2000-April 2003 to characterize the relationship between the status of carotenoids, vitamin E, and retinol and anthropometric status in apparently healthy infants and their mothers in Blantyre, Malawi. Anthropometric status of infants and concentrations of carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin, and lycopene), retinol, and alpha-tocopherol in plasma were measured in 173 infants at 12 months of age, and concentrations of carotenoids, retinol, and a-tocopherol in plasma were measured in their mothers two weeks postpartum. In multivariate analyses, concentrations of retinol, total carotenoids, non-provitamin A carotenoids, and alpha-tocopherol in infants were associated with under-weight (p = 0.05). Concentrations of a-tocopherol were associated with wasting (p = 0.04). Concentrations in mothers and infants were all correlated (correlation coefficients from 0.230 to 0.502, p < 0.003). The findings suggest that poor status of carotenoids, retinol, and alpha-tocopherol in infants is associated with their poor anthropometric status, and status of carotenoids, retinol, and alpha-tocopherol in mothers and infants has a low-to-moderate association in the mother-infant dyad.

Effect of HIV-1 antiretroviral prophylaxis on hepatic and hematological parameters of African infants.

OBJECTIVE: To measure hepatic and hematological parameters among neonates randomized to receive ultra-short antiretroviral regimens. DESIGN: As part of an on-going clinical trial in Malawi, infants born to women who received (early presenters) or did not receive (late presenters) standard intrapartum nevirapine (NVP) dosing were randomized to receive orally either single dose NVP alone or NVP plus zidovudine (twice daily for 1 week). An additional group of untreated infants (born to HIV-uninfected women) was enrolled as a control. METHODS: Laboratory measurements were performed at birth and repeated at 6 weeks of age. Serum alanine aminotransferase (ALT) was measured on approximately 200 infants consecutively enrolled and randomized at the start of the trial. Complete blood count (CBC) was performed on approximately 800 infants at birth and 600 infants at 6 weeks of age. ALT and CBC were also determined on approximately 200 control infants. RESULTS: At birth there were no differences in ALT values between the groups of children. At 6 weeks of age, ALT levels were significantly higher among the treated groups compared with control group (geometric mean of 11.5 U/l for controls and 16.2-19.1 U/l for treated groups; P < 0.0001). Hematological parameters did not differ between groups at birth. At 6 weeks of age, levels of hemoglobin, hematocrit, granulocytes, and platelets were significantly (P < 0.0001) lower among antiviral drug-treated groups compared with controls. These changes were consistent with grade 1 (mild) toxicity, and were more noticeable among HIV-infected infants. CONCLUSIONS: Hepatic and hematologic abnormalities associated with short-term neonatal antiretrovirals among African children are minimal.

The effect of Plasmodium falciparum malaria on peripheral and placental HIV-1 RNA concentrations in pregnant Malawian women.

OBJECTIVE: To investigate the effect of placental Plasmodium falciparum malaria infection on peripheral and/or placental HIV-1 viral load. DESIGN: A cross-sectional study of HIV-infected pregnant women, with and without placental malaria, delivering at Queen Elizabeth Central Hospital in Malawi. METHODS: Peripheral blood samples were collected from consenting women and tested for HIV. HIV-infected women received nevirapine at the onset of labor. At delivery, placental blood and tissue specimens were collected. HIV-1 RNA concentrations were measured in peripheral and placental plasma samples, and malaria infection was determined by placental histopathology. RESULTS: Of the 480 HIV-infected women enrolled, 304 had placental histopathology performed, of whom 74 (24.3%) had placental malaria. Compared with women without placental malaria, those with placental malaria had a 2.5-fold higher geometric mean peripheral HIV-1 RNA concentration (62,359 versus 24 814 copies/ml; P = 0.0007) and a 2.4-fold higher geometric mean placental HIV-1 RNA concentration (11,733 versus 4919 copies/ml; P = 0.008). In multivariate analyses, after adjusting for CD4 cell count and other covariates, placental malaria was associated with a 1.7-fold increase in geometric mean peripheral HIV-1 RNA concentration (47,747 versus 27,317 copies/ml; P = 0.02) and a 2.0-fold increase in geometric mean placental HIV-1 RNA concentration (9670 versus 4874 copies/ml; P = 0.03). CONCLUSION: Placental malaria infection is associated with an increase in peripheral and placental HIV-1 viral load, which might increase the risk of mother-to-child transmission of HIV.

Placental monocyte infiltrates in response to Plasmodium falciparum malaria infection and their association with adverse pregnancy outcomes.

Maternal anemia and low birth weight (LBW) may complicate malaria in pregnancy, and placental monocyte infiltrates have been associated with LBW, and anecdotally with anemia. We examined placental pathology from 357 Malawian women. Intervillous monocyte infiltrates were frequent in placental malaria and were not seen in uninfected placentas. Histology was grouped according to a 5-point scale. Dense monocyte infiltrates and presence of intramonocytic malaria pigment were associated with anemia and LBW. Of factors associated with LBW and/or anemia in univariate analysis, gravidity (P = 0.002), number of antenatal clinic (ANC) visits (P < 0.001), malaria pigment in fibrin (P = 0.03), and monocyte malaria pigment (P = 0.0001) remained associated with lower birth weight by multivariate analysis. Associated with maternal anemia were HIV infection (P < 0.0001), intervillous monocyte numbers (P < 0.0001), number of ANC visits (P = 0.002), and recent febrile symptoms (P = 0.0001). Pigment-containing placental monocytes are associated with anemia and LBW due to malaria, and may have a causative role in their development.

Evaluation of the OptiMAL rapid antigen test and species-specific PCR to detect placental Plasmodium falciparum infection at delivery.

During pregnancy, Plasmodium falciparum infection of the placenta frequently occurs in the absence of parasites in peripheral blood. We investigated the abilities of the OptiMAL rapid immunochromatographic strip test for P. falciparum lactate dehydrogenase and species-specific PCR performed on peripheral blood to detect placental infection or malaria-associated low birth weight. Of 509 Malawian women screened by microscopy, 76 had malaria infection. Among these 509 women, the frequency of peripheral blood parasitemia was low. The OptiMAL test gave positive results in 37 of 171 women tested (one of whom had placental but not peripheral blood parasitemia) and had sensitivities of 71% for peripheral parasitemia and 38% for placental parasitemia compared to the microscopy values. The specificity for peripheral parasitemia was 94%. In 135 women, PCR had sensitivities of 94% for peripheral blood malaria detected by microscopy and 72% for placental infection. In samples examined by PCR, the prevalence of malaria in peripheral blood increased from 26.7% by microscopy to 51.9%. Women with placental malaria and women with malaria in peripheral blood samples by microscopy or OptiMAL testing, but not women with malaria detected only by PCR, had lower-birth-weight babies than did women without malaria by these criteria. Positive results by PCR in the absence of microscopic parasitemia were not associated with low birth weight. Neither OptiMAL nor PCR testing of peripheral blood is adequately sensitive to detect all placental malaria infection, but a positive result by OptiMAL testing identifies women with a high proportion of low-birth-weight babies.

Antibodies to variant surface antigens of Plasmodium falciparum-infected erythrocytes and adhesion inhibitory antibodies are associated with placental malaria and have overlapping and distinct targets.

We measured antibodies to chondroitin sulfate A (CSA)-binding and placental Plasmodium falciparum-infected red blood cells (PRBCs) among pregnant women with or without placental malaria. Immunoglobulin G to PRBC surface antigens was rare in uninfected primigravidae (3.7%), more prevalent in infected primigravidae (70%; P<.001), and common in infected (77%) and uninfected (83%) multigravidae. Similar patterns were seen for agglutinating antibodies, and antibodies were similar among women with past or active placental infection. PRBC adhesion to CSA was inhibited 60% by serum from infected primigravidae but 24% by serum from uninfected primigravidae (P=.025), whereas infection did not alter adhesion inhibition by multigravidae (77% inhibition)[corrected]. There was substantial heterogeneity in antibody type and levels. Antibodies did not correlate with parasite density or pregnancy outcome. Comparisons between antibodies suggest that adhesion-inhibitory antibodies and those to PRBC variant antigens have distinct and overlapping epitopes, may be acquired independently, and have different roles in immunity.

The risk of human immunodeficiency virus-1 infection in twin pairs born to infected mothers in Africa.

We examined birth order and delivery route as risk factors for mother-to-child transmission of human immunodeficiency virus (HIV)-1 in 315 twin pairs born in Malawi during 1994-1998. No antiretroviral drugs were administered to these subjects. Infections were detected by polymerase chain reaction and were stratified as having occurred either in utero, perinatally, or postnatally. Risk of in utero infection for 630 infants (39 infections) did not differ by birth order (first born, 6.3%; second born, 6.0%). Similarly, in 260 vaginally delivered infants evaluated for perinatal infection (45 infections), risk did not differ by birth order (first born, 15.9%; second born, 18.7%); risk of perinatal infection was significantly lower in cesarean-delivered infants (odds ratio, 0.19 [95% confidence interval, 0.02-0.78]). There was no effect on postnatal transmission rates. Thus, in contrast to the authors of earlier studies, we did not find birth order to be an important risk factor for infection in twins. These findings indicate that birth-canal exposure is not a major contributor to a newborn's risk of HIV-1 infection.

Placental tumor necrosis factor alpha but not gamma interferon is associated with placental malaria and low birth weight in Malawian women.

Malaria in pregnancy predisposes to maternal anemia and low birth weight (LBW). We examined the possible roles of the cytokines tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) in these adverse outcomes. We measured cytokine concentrations in placental, peripheral, and cord blood plasma in relation to malaria parasitemia and placental monocyte accumulation in 276 Malawian women. Maternal hemoglobin concentration, human immunodeficiency virus status, and infant birth weight were determined. Concentrations of TNF-alpha in placental blood were correlated with densities of Plasmodium falciparum-infected erythrocytes (P < 0.0001) and of intervillous monocyte infiltrates (P < 0.0001) on placental histology. Peripheral blood TNF-alpha concentrations were relatively low and were weakly associated with malaria. TNF-alpha concentrations were higher in placental blood, where they were strongly associated with malaria. Placental plasma TNF-alpha levels were higher in women who had LBW babies (P = 0.0027), women with febrile symptoms (P < 0.0001), and teenage mothers (P = 0.04) than in other women. The presence of TNF-alpha in cord blood was not associated with malaria infection. IFN-gamma levels were infrequently elevated, and elevated IFN-gamma levels were not associated with poor pregnancy outcomes. Placental production of TNF-alpha, but not of IFN-gamma, may be implicated in impaired fetal growth in Malawian women.

Host response to malaria during pregnancy: placental monocyte recruitment is associated with elevated beta chemokine expression.

Malaria during pregnancy is associated with poor birth outcomes, particularly low birth weight. Recently, monocyte infiltration into the placental intervillous space has been identified as a key risk factor for low birth weight. However, the malaria-induced chemokines involved in recruiting and activating placental monocytes have not been identified. In this study, we determined which chemokines are elevated during placental malaria infection and the association between chemokine expression and placental monocyte infiltration. Placental malaria infection was associated with elevations in mRNA expression of three beta chemokines, macrophage-inflammatory protein 1 (MIP-1) alpha (CCL3), monocyte chemoattractant protein 1 (MCP-1; CCL2), and I-309 (CCL1), and one alpha chemokine, IL-8 (CXCL8); all correlated with monocyte density in the placental intervillous space. Placental plasma concentrations of MIP-1 alpha and IL-8 were increased in women with placental malaria and were associated with placental monocyte infiltration. By immunohistochemistry, we localized placental chemokine production in malaria-infected placentas: some but not all hemozoin-laden maternal macrophages produced MIP-1 beta and MCP-1, and fetal stromal cells produced MCP-1. In sum, local placental production of chemokines is increased in malaria, and may be an important trigger for monocyte accumulation in the placenta.

Risk factors and mechanisms of preterm delivery in Malawi.

PROBLEM: We examined risk factors and mechanisms of preterm delivery (PTD) in malaria-exposed pregnant women in Blantyre, Malawi. METHOD OF STUDY: The human immunodeficiency virus (HIV), malaria, syphilis, and anemia were assessed in a cross-sectional study of 572 pregnant women. In a nested case-control study, chorioamnionitis (CAM) was examined; tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, macrophage inflammatory protein (MIP)-1alpha, monocyte chemotactic protein (MCP)-1, transforming growth factor (TGF)-beta, cortisol, and corticotropin-releasing hormone were measured in placental, maternal and/or cord blood. RESULTS: HIV, infrequent antenatal clinic attendance, low-maternal weight, no intermittent preventive malaria therapy (IPT), and CAM were associated with PTD, while malaria was not. Of the 18 compartmental cytokine measurements, elevations in placental and/or cord IL-6 and IL-8 were associated with both CAM and PTD. In contrast, there was no overlap between the cytokines affected by malaria and those associated with PTD. CONCLUSIONS: The HIV and CAM were the major infections associated with PTD in this study. CAM, but not malaria, causes PTD via its effect on proinflammatory cytokines.