Timing of the human prenatal antibody response to Plasmodium falciparum antigens.

Plasmodium falciparum (Pf)-specific T- and B-cell responses may be present at birth; however, when during fetal development antibodies are produced is unknown. Accordingly, cord blood samples from 232 preterm (20-37 weeks of gestation) and 450 term (≥37 weeks) babies were screened for IgM to Pf blood-stage antigens MSP1, MSP2, AMA1, EBA175 and RESA. Overall, 25% [95% CI = 22-28%] of the 682 newborns were positive for IgM to ≥1 Pf antigens with the earliest response occurring at 22 weeks. Interestingly, the odds of being positive for cord blood Pf IgM decreased with gestational age (adjusted OR [95% CI] at 20-31 weeks = 2.55 [1.14-5.85] and at 32-36 weeks = 1.97 [0.92-4.29], with ≥37 weeks as reference); however, preterm and term newborns had similar levels of Pf IgM and recognized a comparable breadth of antigens. Having cord blood Pf IgM was associated with placental malaria (adjusted OR [95% CI] = 2.37 [1.25-4.54]). To determine if in utero exposure occurred via transplacental transfer of Pf-IgG immune complexes (IC), IC containing MSP1 and MSP2 were measured in plasma of 242 mother-newborn pairs. Among newborns of IC-positive mothers (77/242), the proportion of cord samples with Pf IC increased with gestational age but was not associated with Pf IgM, suggesting that fetal B cells early in gestation had not been primed by IC. Finally, when cord mononuclear cells from 64 term newborns were cultured in vitro, only 11% (7/64) of supernatants had Pf IgM; whereas, 95% (61/64) contained secreted Pf IgG. These data suggest fetal B cells are capable of making Pf-specific IgM from early in the second trimester and undergo isotype switching to IgG towards term.

Comparison of the specificity of antibodies to VAR2CSA in Cameroonian multigravidae with and without placental malaria: a retrospective case-control study.

BACKGROUND: Antibodies (Ab) to VAR2CSA prevent Plasmodium falciparum-infected erythrocytes from sequestrating in the placenta, i.e., prevent placental malaria (PM). The specificity of Ab to VAR2CSA associated with absence of PM is unknown. Accordingly, differences in the specificity of Ab to VAR2CSA were compared between multigravidae with and without PM who had Ab to VAR2CSA. METHODS: In a retrospective case-control study, plasma collected from Cameroonian multigravidae with (n = 96) and without (n = 324) PM were screened in 21 assays that measured antibody levels to full length VAR2CSA (FV2), individual VAR2CSA DBL domains, VAR2CSA domains from different genetic backgrounds (variants), as well as proportion of high avidity Ab to FV2. RESULTS: Multigravidae with and without PM had similar levels of Ab to FV2, the six VAR2CSA DBL domains and different variants, while the proportion of high avidity Ab to FV2 was significantly higher in women without PM at delivery (p = 0.0030) compared to women with PM. In a logistic regression model adjusted for gravidity and age, the percentage of high avidity Ab to FV2 was associated with reduced likelihood of PM in multigravidae. A 5 % increase in proportion of high avidity Ab to FV2 was associated with a nearly 15 % lower likelihood of PM. CONCLUSION: Ab avidity to FV2 may be an important indicator of immunity to PM.

The impact of signing a memorandum of understanding on reproductive health with the Ministry of Public Health in Cameroon.

Health statistics relating to Millennium Development Goals 4 and 5 are poor for most low-resource countries. Professional societies can assist governments to improve these health indicators. For an effective collaboration, the Society of Gynaecologists and Obstetricians Cameroon (SOGOC) and the Ministry of Public Health signed a memorandum of understanding on reproductive health. A major consequence of this collaboration was the ease of transfer of competence associated with SOGOC adopting a monitoring and evaluation role, which has improved quality of care. The impact of this collaboration for the Society has been significant; SOGOC is recognized as a partner and has an opportunity to play a leadership role in issues concerning reproductive health.

Expanding the use of manual vacuum aspiration for incomplete abortion in selected health institutions in Yaoundé, Cameroon.

Preference for manual vacuum aspiration (MVA) and its use for the treatment of incomplete abortion were evaluated among 52 healthcare professionals in 7 Yaoundé hospitals in Cameroon. All but one healthcare professional preferred MVA; however, this technique was available at all times in only two hospitals. In some hospitals, MVA use was only available during the day, while in others it was not available at all. Based on these findings, MVA kits were obtained from the International Federation of Gynecology and Obstetrics (FIGO) for training and to supply selected hospitals. The result was a dramatic increase in the use of MVA in all of the hospitals that received the kits. In one hospital, no kits were received; however, the staff had been sensitized to the problem and the equipment belonging to one of the physicians was put into service. The successful experience of this pilot project provides a rationale for expanding MVA use for incomplete abortion to the entire country.

Contribution of obstetrics and gynecology societies in West and Central African countries to the prevention of unsafe abortion.

Unsafe abortion is a major public health issue in low-resource countries. In the countries of West and Central Africa, abortion-related maternal mortality rates are extremely high, the prevalence of modern contraceptive use is very low, and the unmet need for family planning is also high. The International Federation of Gynecology and Obstetrics (FIGO) Initiative for the Prevention of Unsafe Abortion and its Consequences has contributed substantially toward increasing awareness of the problem of abortion, bringing abortion-related issues to the attention of the professional societies, individual gynecologists and obstetricians, Ministries of Health, healthcare providers, and to the community in general. The promotion of quality postabortion care including the use of manual vacuum aspiration, misoprostol, and postabortion contraception has greatly improved access to services; however, there is still a long way to go.

The antibody response of pregnant Cameroonian women to VAR2CSA ID1-ID2a, a small recombinant protein containing the CSA-binding site.

In pregnant women, Plasmodium falciparum-infected erythrocytes expressing the VAR2CSA antigen bind to chondroitin sulfate A in the placenta causing placental malaria. The binding site of VAR2CSA is present in the ID1-ID2a region. This study sought to determine if pregnant Cameroonian women naturally acquire antibodies to ID1-ID2a and if antibodies to ID1-ID2a correlate with absence of placental malaria at delivery. Antibody levels to full-length VAR2CSA and ID1-ID2a were measured in plasma samples from 745 pregnant Cameroonian women, 144 Cameroonian men, and 66 US subjects. IgM levels and IgG avidity to ID1-ID2a were also determined. As expected, antibodies to ID1-ID2a were absent in US controls. Although pregnant Cameroonian women developed increasing levels of antibodies to full-length VAR2CSA during pregnancy, no increase in either IgM or IgG to ID1-ID2a was observed. Surprisingly, no differences in antibody levels to ID1-ID2a were detected between Cameroonian men and pregnant women. For example, in rural settings only 8-9% of males had antibodies to full-length VAR2CSA, but 90-96% had antibodies to ID1-ID2a. In addition, no significant difference in the avidity of IgG to ID1-ID2a was found between pregnant women and Cameroonian men, and no correlation between antibody levels at delivery and absence of placental malaria was found. Thus, the response to ID1-ID2a was not pregnancy specific, but predominantly against cross-reactivity epitopes, which may have been induced by other PfEMP1 antigens, malarial antigens, or microbes. Currently, ID1-ID2a is a leading vaccine candidate, since it binds to the CSA with the same affinity as the full-length molecule and elicits binding-inhibitory antibodies in animals. Further studies are needed to determine if the presence of naturally acquired cross-reactive antibodies in women living in malaria endemic countries will alter the response to ID1-ID2a following vaccination with ID1-ID2a.

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)-ß 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.

The FIGO working group on the prevention of unsafe abortion: mandate and process for achievement.

The Working Group of the International Federation of Gynecology and Obstetrics (FIGO) on the Prevention of Unsafe Abortion and its Consequences received a mandate to contribute to reduce the number of women who have to resort to induced abortion and the maternal mortality and morbidity associated with unsafe abortion by minimizing unintended pregnancies, improving access to safe abortion services, and increasing the quality of and access to post-abortion care, including post-abortion contraception. A project proposal was prepared and approved by an anonymous donor, funding a structure headed by a general coordinator, the Chair of the Working Group, together with 6 regional coordinators and 1 assistant regional coordinator, plus 43 focal points nominated by the participating societies. A situational analysis of induced/unsafe abortion for each country was prepared by the focal points with the technical support of the Guttmacher Institute, and a plan of action based on the findings of the analysis. The situational analysis and plans of action were discussed at 7 regional workshops held between June and August, 2008. Fifty-four member societies nominated a focal point, 48 attended the regional workshops, and 43 had a plan of action approved by their governments and respective societies. The plans of action are currently in the process of implementation, with the collaboration of a number of national and international agencies and organizations.

International organizations and NGOs: an example of international collaboration to improve women's health by preventing unsafe abortion.

International collaboration with organizations and agencies is a basic requirement for the success of the FIGO Initiative for the Prevention of Unsafe Abortion and its Consequences. Many activities being carried out by the organizations form a part of the plans of action of all countries participating in the Initiative. It was, therefore, not difficult to obtain their collaboration in implementing the plans of action. The many ways in which they have collaborated and continue to do so are described in this article. This collaboration has saved time, avoided duplication of effort, and has also satisfied the Accra Agenda of Action by reducing fragmentation of funding. It has already contributed toward preventing unsafe abortion and reducing abortion-related maternal deaths and morbidities, and is expected to contribute even more significantly in the coming months and years.

Acceptability of intrapartum HIV counselling and testing in Cameroon.

BACKGROUND: To assess the acceptability of intrapartum HIV testing and determine the prevalence of HIV among labouring women with unknown HIV status in Cameroon. METHOD: The 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. RESULTS: A 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. CONCLUSION: Acceptability 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.

Gynaecological morbidity among HIV positive pregnant women in Cameroon.

OBJECTIVE: To compare the prevalence of gynaecological conditions among HIV infected and non-infected pregnant women. METHODS: Two thousand and eight (2008) pregnant women were screened for HIV, lower genital tract infections and lower genital tract neoplasia at booking antenatal visit. RESULTS: About 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). CONCLUSION: We 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.

Mother-to-child transmission of human immunodeficiency virus type 1 in relation to the season in Yaounde, Cameroon.

A public health program to prevent mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) by treatment with nevirapine has been ongoing in Yaounde, Cameroon since January 2000. After 24 months, plasma samples from 119 children born to HIV-1-positive mothers were tested for HIV-1 RNA between six and eight weeks after birth. Thirteen (10.9%) tested positive (95% confidence interval = 5.2-16.7%). Risk factors associated with MTCT in this study were maternal viral load (P < 0.05), low birth weight (chi2 for trend = 8.78, P = 0.01), and birth during the second half of the year. A high correlation was repeatedly observed between rainfall in a given month and the risk of MTCT of HIV-1 in children born three months later (r = 0.634, P < 0.001). Although we cannot rule out other tropical infections related to the rainy season, the role of malaria is highly suspected since the interval of three months we observed between the peaks of rainfall and the rate of transmission is consistent with the Plasmodium life cycle.

Congenital exposure to Plasmodium falciparum antigens: prevalence and antigenic specificity of in utero-produced antimalarial immunoglobulin M antibodies.

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.

Malaria-associated cytokine changes in the placenta of women with pre-term deliveries in Yaounde, Cameroon.

The prevalence of pre-term deliveries (PTDs) is increased in women who become infected with Plasmodium falciparum during pregnancy. Because prematurity is a risk factor for newborns, it is important to identify conditions that contribute to malaria-associated PTDs. Plasmodium falciparum-infected erythrocytes sequester in the placenta and attract activated mononuclear cells that secrete pro-inflammatory cytokines. Increased inflammatory cytokine levels in other microbial infections are associated with PTDs. To determine if such is the case in women with placental malaria, concentrations of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4), and IL-10 were measured in placental plasma of 391 malaria-infected and -uninfected Cameroonian women with premature and full-term deliveries. Risk factors for malaria-associated PTDs included peripheral and placental parasitemias greater than 1%, maternal anemia, elevated IL-10 levels, and low TNF-alpha:IL-10 ratios due to over-expression of IL-10. Alterations in cytokine levels may contribute to PTDs through the induction of anemia and/or altering cellular immune responses required for eliminating placental parasites.