VAR2CSA mediates sequestration of Plasmodium falciparum-infected erythrocytes in the placenta, increasing the risk of poor pregnancy outcomes. Naturally acquired antibodies (Ab) to placental parasites at delivery have been associated with improved pregnancy outcomes, but Ab levels and how early in pregnancy Ab must be present in order to eliminate placental parasites before delivery remains unknown. Antibodies to individual Duffy-binding like domains of VAR2CSA have been studied, but the domains lack many of the conformational epitopes present in full-length VAR2CSA (FV2). Thus, the purpose of this study was to describe the acquisition of Ab to FV2 in women residing in high and low transmission areas and determine how Ab levels during pregnancy correlate with clearance of placental parasites. Plasma samples collected monthly throughout pregnancy from pregnant women living in high and low transmission areas in Cameroon were evaluated for Ab to FV2 and the proportion of high avidity Ab (i.e., Ab that remain bound in the presence of 3M NH4SCN) was assessed. Ab levels and proportion of high avidity Ab were compared between women with placental malaria (PM+) and those without (PM−) at delivery. Results showed that PM− women had significantly higher Ab levels (p = 0.0047) and proportion of high avidity Ab (p = 0.0009) than PM+ women throughout pregnancy. Specifically, women with moderate to high Ab levels (>5,000 MFI) and those with ≥35% high avidity Ab at 5–6 months were found to have 2.3 (95% CI, 1.0–4.9) and 7.6-fold (p = 0.0013, 95% CI: 1.2–50.0) reduced risk of placental malaria, respectively. These data show that high levels of Ab to FV2, particularly those with high avidity for FV2, produced by mid-pregnancy are important in clearing parasites from the placenta. Both high Ab levels and proportion of high avidity Ab to FV2 may serve as correlates of protection for assessing immunity against placental malaria.

Plasmodium falciparum-infected erythrocytes (IEs) sequester in the intervillous space (IVS) of the placenta causing placental malaria (PM), a condition that increases a woman’s chances of having a low-birth-weight baby. Because IEs sequester, they frequently are not observed in peripheral blood smears, resulting in women with PM being misdiagnosed and thus not treated. Because sequestered IEs induce inflammation in the IVS, detection of inflammatory mediators in the peripheral blood may provide an approach for diagnosing PM. Two counterregulatory molecules, TNF-αR (TNFR) 1 and TNFR2, modulate the pathological effects of TNF-α. Levels of these soluble TNFRs (sTNFRs) are reported to be elevated in children with severe malaria, but it is unclear if they are increased in the peripheral blood of PM-positive women with asymptomatic infections. In this study, sTNFR levels were measured throughout the course of pregnancy, as well as at delivery, in women with asymptomatic infections and those who remained uninfected. Results showed that both sTNFRs were significantly increased in the peripheral blood of women with asymptomatic malaria (p < 0.0001) and were positively correlated with parasitemia (p < 0.0001 for sTNFR1 and p = 0.0046 for sTNFR2). Importantly, levels of sTNFR2 were elevated in the peripheral blood of women who were PM-positive but peripheral blood-smear negative (p = 0.0017). Additionally, sTNFR2 levels were elevated in the blood of malaria-positive women who delivered low-birth-weight babies. In vitro studies demonstrated that syncytiotrophoblasts were not a major source of sTNFR. These data suggest that sTNFR2 may be a valuable biomarker for detection of malaria-associated inflammation.

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Hepatotoxicity is historically the 3rd most common reason for drug withdrawal and toxicity-related discontinuation of treatment. This study was aimed at determining the incidence and the onset of hepatotoxicity and at evaluating the relationship of some risk factors for hepatotoxicity among Human Immunodeficiency Virus- (HIV-) positive, tuberculosis (TB), and HIV/TB patients on treatment. This was a prospective follow-up study involving 125 participants from the HIV/AIDS and TB treatment centres in three hospitals in Fako Division of Cameroon. These TB and HIV patients were initiated on RHEZ (R = Rifampicin, H = Isoniazid, E = Ethambutol, and P = Pyrazinamide) and TELE (efavirenz/tenofovir/lamivudine), respectively, and followed up for 12 weeks between September 2018 and November 2019. The levels of liver enzymes (transaminases, gamma-glutamyltransferase, alkaline phosphatase, and unconjugated/total bilirubin) were measured spectrophotometrically using serum. The Chi-squared (χ2) test was used to assess the association between risk factors and hepatotoxicity, while the Kaplan-Meier survival analysis with the log-rank test was used to determine the occurrence of hepatotoxicity in the different groups. We followed the general study population for a total person time of 6580 person-days, with an incidence rate and cumulative incidence of 8 cases per 1000 person-days (53/6580 person-days) and 42.4% (53/125), respectively (95% confidence interval), recorded after 12 weeks of follow-up of all the participants. The onset of hepatotoxicity in the total study population was statistically significant (χ2=9.5334; p=0.022979; CI=95%), with the majority observed at week eight of follow-up. Also, the incidence rate and cumulative incidence of hepatotoxicity with respect to HIV/AIDS, TB, and HIV/TB patients, respectively, at 95% confidence interval were: 8 cases per 1000 person-days (32/3843 person-days) and 32/76 (42.1%), 6 cases per 1000 person-days (12/1932 person-days) and 12/32 (37.5%), and 11 cases per 1000 person-days (9/805 person-days) and 9/17 (52.9%). This study shows that the incidence rate and cumulative incidence of hepatotoxicity in HIV/AIDS, TB, and HIV/TB patients on treatment were high in Fako Division, Cameroon. Also, it is very important to check these patients’ liver function especially within the first 12 weeks of treatment.

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