Robert J. I. Leke

High Levels of Antibodies to Multiple Domains and Strains of VAR2CSA Correlate with the Absence of Placental Malaria in Cameroonian Women Living in an Area of High Plasmodium falciparum Transmission

ABSTRACT Placental malaria, caused by sequestration of Plasmodium falciparum-infected erythrocytes in the placenta, is associated with increased risk of maternal morbidity and poor birth outcomes. The parasite antigen VAR2CSA (variant surface antigen 2-chondroitin sulfate A) is expressed on infected erythrocytes and mediates binding to chondroitin sulfate A, initiating inflammation and disrupting homeostasis at the maternal-fetal interface. Although antibodies can prevent sequestration, it is unclear whether parasite clearance is due to antibodies to a single Duffy binding-like (DBL) domain or to an extensive repertoire of antibodies to multiple DBL domains and allelic variants. Accordingly, plasma samples collected longitudinally from pregnant women were screened for naturally acquired antibodies against an extensive panel of VAR2CSA proteins, including 2 to 3 allelic variants for each of 5 different DBL domains. Analyses were performed on plasma samples collected from 3 to 9 months of pregnancy from women living in areas in Cameroon with high and low malaria transmission. The results demonstrate that high antibody levels to multiple VAR2CSA domains, rather than a single domain, were associated with the absence of placental malaria when antibodies were present from early in the second trimester until term. Absence of placental malaria was associated with increasing antibody breadth to different DBL domains and allelic variants in multigravid women. Furthermore, the antibody responses of women in the lower-transmission site had both lower magnitude and lesser breadth than those in the high-transmission site. These data suggest that immunity to placental malaria results from high antibody levels to multiple VAR2CSA domains and allelic variants and that antibody breadth is influenced by malaria transmission intensity.

Congenital Exposure to Plasmodium falciparum Antigens: Prevalence and Antigenic Specificity of In Utero-Produced Antimalarial Immunoglobulin M Antibodies

ABSTRACT Congenital Plasmodium falciparum malaria in newborns is uncommon in sub-Saharan Africa. A significant number of infants, however, become infected or exposed to malarial antigens either in utero or at delivery and have the potential to produce antimalarial antibodies and memory cells before their first natural infection. In Yaounde, Cameroon, parasite-specific immunoglobulin M (IgM) was detected in 14% of cord blood samples. The IgM antibodies reacted with a wide range of asexual-stage antigens, with each newborn having its own unique pattern of IgM reactivity. PCR-based detection and genotyping of cord blood parasites found that the prevalence, total number of parasite genotypes, and complexity of infection were higher in newborns who had produced antimalarial IgM than those who had not. Maternal placental malaria and anemia were associated with the production of P. falciparum-specific IgM by the fetus. The effect of early immune priming on acquisition of immunity by infants is unknown and merits further investigation, since a significant proportion of Cameroonian newborns developed a humoral response to malaria before birth.

Ectopic pregnancy in African developing countries

Objective. We have reviewed the scientific literature on ectopic pregnancy (EP) in African countries published over the past 20 years and available from several databases (MEDLINE, EMBASE, POPLINE, and Cochrane Fertility Regulation Group), with the aim of painting a complete picture of the situation (incidence, risk factors, diagnosis, treatment, and complications).

Ectopic pregnancy in Africa: a population-based study.

OBJECTIVE: To estimate the incidence of ectopic pregnancy in Yaounde, the capital of Cameroon (Central Africa). METHODS: In 2000, all women admitted for an ectopic pregnancy to health facilities in the city of Yaounde were systematically enrolled. Sociodemographic information on the women and their reproductive history was collected by questionnaire during a face-to-face interview. Medical and obstetrical data (clinical findings at hospital entry, medical history, type of surgery, and final vital status) were collected from gynecologic and surgical files and admission registers. RESULTS: We recorded 320 cases of ectopic pregnancy in health facilities in the city of Yaounde and we estimated that 40,100 live births occurred during the same study period (January to December 2000). The population-based incidence rate of ectopic pregnancy in the city of Yaounde was 0.79% (95% confidence interval 0.72%, 0.88%) in 2000. Three maternal deaths were recorded giving a mortality rate of 0.94% (95% confidence interval 0.32%, 2.72%). CONCLUSION: The 0.79% ectopic pregnancy incidence rate observed in this African country must be considered a minimum due to probable underestimation. Nevertheless, this rate is lower than that currently observed in industrialized countries. Late diagnosis, low percentage of conservative treatment, and subsequent maternal deaths are important findings that should encourage African gynecologists to promote ectopic pregnancy prevention programs and to improve the care given to women with ectopic pregnancy. LEVEL OF EVIDENCE: III

Complications of induced abortion and miscarriage in three African countries : a hospital-based study among WHO collaborating centers.

Objective. The aim of this study was to describe two of the outcomes of pregnancy, induced abortion and miscarriage, in three African countries. Major maternal risk factors were also evaluated.

Circulating soluble endoglin levels in pregnant women in Cameroon and Malawi--associations with placental malaria and fetal growth restriction.

Placental infections with Plasmodium falciparum are associated with fetal growth restriction resulting in low birth weight (LBW). The mechanisms that mediate these effects have yet to be completely described; however, they are likely to involve inflammatory processes and dysregulation of angiogenesis. Soluble endoglin (sEng), a soluble receptor of transforming growth factor (TGF)-β previously associated with preeclampsia in pregnant women and with severe malaria in children, regulates the immune system and influences angiogenesis. We hypothesized that sEng may play a role in development of LBW associated with placental malaria (PM). Plasma levels of sEng were measured in women (i) followed prospectively throughout pregnancy in Cameroon (n = 52), and (ii) in a case-control study at delivery in Malawi (n = 479). The relationships between sEng levels and gravidity, peripheral and placental parasitemia, gestational age, and adverse outcomes of PM including maternal anemia and LBW were determined. In the longitudinal cohort from Cameroon, 28 of 52 women (54%) experienced at least one malaria infection during pregnancy. In Malawi we enrolled two aparasitemic gravidity-matched controls for every case with PM. sEng levels varied over the course of gestation and were significantly higher in early and late gestation as compared to delivery (P<0.006 and P<0.0001, respectively). Circulating sEng levels were higher in primigravidae than multigravidae from both Cameroon and Malawi, irrespective of malarial infection status (p<0.046 and p<0.001, respectively). Peripheral parasitemia in Cameroonian women and PM in Malawian women were each associated with elevated sEng levels following correction for gestational age and gravidity (p = 0.006 and p = 0.033, respectively). Increased sEng was also associated with the delivery of LBW infants in primigravid Malawian women (p = 0.017); the association was with fetal growth restriction (p = 0.003) but not pre-term delivery (p = 0.286). Increased circulating maternal sEng levels are associated with P. falciparum infection in pregnancy and with fetal growth restriction in primigravidae with PM.

Longitudinal studies of Plasmodium falciparum malaria in pregnant women living in a rural Cameroonian village with high perennial transmission.

A prospective longitudinal study of Plasmodium falciparum in pregnant women was conducted in the rural village of Ngali II, where malaria is hyperendemic and individuals receive ~0.7 infectious mosquito bites/person/day throughout the year. Pregnant women (N = 60; 19 primigravidae, 41 multigravidae) were enrolled early in pregnancy (median 14 wk) and were followed monthly, with 38 women followed through term (5.7 ± 1.1 prenatal visits and delivery). The total number of times primigravidae were slide-positive during pregnancy was higher than multigravidae (3.3 ± 1.1 versus 1.3 ± 1.3 times; P < 0.001), but no difference in the number of polymerase chain reaction-positive cases (4.6 ± 1.7 and 3.4 ± 1.7 times, P = 0.106) or total genotypes they harbored (8.9 ± 3.2 and 7.0 ± 2.9) was found. Only 7.9% women developed symptomatic infections. All primigravidae and 38% multigravidae were placental malaria-positive at delivery (P = 0.009). Genotyping showed that 77% of placental parasites were acquired ≥ 30 wks in pregnancy. These results help identify the extent of malaria-associated changes women experience during pregnancy.

Gynaecological morbidity among HIV positive pregnant women in Cameroon

ObjectiveTo compare the prevalence of gynaecological conditions among HIV infected and non-infected pregnant women.MethodsTwo thousand and eight (2008) pregnant women were screened for HIV, lower genital tract infections and lower genital tract neoplasia at booking antenatal visit.ResultsAbout 10% (198/2008) were HIV positive. All lower genital tract infections except candidiasis were more prevalent among HIV positive compared to HIV negative women: vaginal candidiasis (36.9% vs 35.4%; p = 0.678), Trichomoniasis (21.2% vs 10.6%; p < 0.001), gonorrhoea (10.1% vs 2.5%; p < 0.001), bacterial vaginosis (21.2% vs 15.2%; p = 0.026), syphilis (35.9% vs 10.6%; p < 0.001), and Chlamydia trachomatis (38.4% vs 7.1%; p < 0.001). Similarly, HIV positive women more likely to have preinvasive cervical lesions: low-grade squamous intraepithelial lesion (SIL) (18.2% vs 4.4%; p < 0.001) and high-grade squamous intraepithelial lesion (12.1% vs 1.5%; p < 0.001).ConclusionWe conclude that (i) sexually transmitted infections (STIs) are common in both HIV positive and HIV negative pregnant women in Cameroon, and (ii) STIs and preinvasive cervical lesions are more prevalent in HIV-infected pregnant women compared to their non-infected compatriots. We recommend routine screening and treatment of STIs during antenatal care in Cameroon and other countries with similar social profiles.

The risk approach for reducing maternal mortality: the Yaounde experience

A review of the strategy of the risk approach to maternal care in the obstetrics and gynecology services of CUSS over a 12‐year period has been reported. By combining antepartum, intrapartum, and postpartum family planning components and by a rational deployment of personnel and restricted resources, the maternal mortality ratio was decreased by up to 60% in one unit and maintained at 0–0.84 per 1000 in the other unit. The package is proposed as a prototype for Africa and the developing world.

Acceptability of intrapartum HIV counselling and testing in Cameroon

BackgroundTo assess the acceptability of intrapartum HIV testing and determine the prevalence of HIV among labouring women with unknown HIV status in Cameroon.MethodThe study was conducted in four hospitals (two referral and two districts hospitals) in Cameroon. Labouring women with unknown HIV status were counselled and those who accepted were tested for HIV.ResultsA total of 2413 women were counselled and 2130 (88.3%) accepted to be tested for HIV. Of the 2130 women tested, 214 (10.1%) were HIV positive. Acceptability of HIV testing during labour was negatively associated with maternal age, parity and number of antenatal visits, but positively associated with level of education. HIV sero-status was positively associated with maternal age, parity, number of antenatal visits and level education.ConclusionAcceptability of intrapartum HIV testing is high and the prevalence of HIV is also high among women with unknown HIV sero-status in Cameroon. We recommend an opt-out approach (where women are informed that HIV testing will be routine during labour if HIV status is unknown but each person may decline to be tested) for Cameroon and countries with similar social profiles.