Background Pregnant and lactating women were excluded from initial COVID-19 vaccine trials; thus, data to guide vaccine decision-making are lacking. Objectives To evaluate the immunogenicity and reactogenicity of COVID-19 mRNA vaccination in pregnant and lactating women compared to: (1) non-pregnant controls and (2) natural COVID-19 infection in pregnancy. Study Design 131 reproductive-age vaccine recipients (84 pregnant, 31 lactating, and 16 non-pregnant) were enrolled in a prospective cohort study at two academic medical centers. Titers of SARS-CoV-2 Spike and RBD IgG, IgA and IgM were quantified in participant sera (N=131) and breastmilk (N=31) at baseline, second vaccine dose, 2-6 weeks post second vaccine, and at delivery by Luminex. Umbilical cord sera (N=10) titers were assessed at delivery. Titers were compared to those of pregnant women 4-12 weeks from natural infection (N=37) by ELISA. A pseudovirus neutralization assay was used to quantify neutralizing antibody titers for the subset of women who delivered during the study period. Post-vaccination symptoms were assessed via questionnaire. Kruskal-Wallis tests and a mixed effects model, with correction for multiple comparisons, were used to assess differences between groups. Results Vaccine-induced antibody titers were equivalent in pregnant and lactating compared to non-pregnant women (median [IQR] 5.59 [4.68-5.89] pregnant, 5.74 [5.06-6.22] lactating, 5.62 [4.77-5.98] non-pregnant, p = 0.24). All titers were significantly higher than those induced by SARS-CoV-2 infection during pregnancy (p < 0.0001). Vaccine-generated antibodies were present in all umbilical cord blood and breastmilk samples. Neutralizing antibody titers were lower in umbilical cord compared to maternal sera, although this finding did not achieve statistical significance (median [IQR] 104.7 [61.2-188.2] maternal sera, 52.3 [11.7-69.6] cord sera, p=0.05). The second vaccine dose (boost dose) increased SARS-CoV-2-specific IgG, but not IgA, in maternal blood and breastmilk. No differences were noted in reactogenicity across the groups. Conclusions COVID-19 mRNA vaccines generated robust humoral immunity in pregnant and lactating women, with immunogenicity and reactogenicity similar to that observed in non-pregnant women. Vaccine-induced immune responses were significantly greater than the response to natural infection. Immune transfer to neonates occurred via placenta and breastmilk.

SARS-CoV-2 infection causes more severe disease in pregnant women compared to age-matched non-pregnant women. Whether maternal infection causes changes in the transfer of immunity to infants remains unclear. Maternal infections have previously been associated with compromised placental antibody transfer, but the mechanism underlying this compromised transfer is not established. Here, we used systems serology to characterize the Fc-profile of influenza-, pertussis-, and SARS-CoV-2-specific antibodies transferred across the placenta. Influenza- and pertussis-specific antibodies were actively transferred. However, SARS-CoV-2-specific antibody transfer was significantly reduced compared to influenza- and pertussis-specific antibodies, and cord titers and functional activity were lower than in maternal plasma. This effect was only observed in third trimester infection. SARS-CoV-2-specific transfer was linked to altered SARS-CoV-2-antibody glycosylation profiles and was partially rescued by infection-induced increases in IgG and increased FCGR3A placental expression. These results point to unexpected compensatory mechanisms to boost immunity in neonates, providing insights for maternal vaccine design.

Background: Pregnant and lactating women were excluded from initial COVID-19 vaccine trials; thus, data to guide vaccine decision-making are lacking. We sought to evaluate the immunogenicity and reactogenicity of COVID-19 mRNA vaccination in pregnant and lactating women. Methods: 131 reproductive-age vaccine recipients (84 pregnant, 31 lactating, and 16 non-pregnant) were enrolled in a prospective cohort study at two academic medical centers. Titers of SARS-CoV-2 Spike and RBD IgG, IgA and IgM were quantified in participant sera (N=131), umbilical cord sera (N=10), and breastmilk (N=31) at baseline, 2nd vaccine dose, 2-6 weeks post 2nd vaccine, and delivery by Luminex, and confirmed by ELISA. Titers were compared to pregnant women 4-12 weeks from native infection (N=37). Post-vaccination symptoms were assessed. Kruskal-Wallis tests and a mixed effects model, with correction for multiple comparisons, were used to assess differences between groups. Results: Vaccine-induced immune responses were equivalent in pregnant and lactating vs non-pregnant women. All titers were higher than those induced by SARS-CoV-2 infection during pregnancy. Vaccine-generated antibodies were present in all umbilical cord blood and breastmilk samples. SARS-CoV-2 specific IgG, but not IgA, increased in maternal blood and breastmilk with vaccine boost. No differences were noted in reactogenicity across the groups. Conclusions: COVID-19 mRNA vaccines generated robust humoral immunity in pregnant and lactating women, with immunogenicity and reactogenicity similar to that observed in non-pregnant women. Vaccine-induced immune responses were significantly greater than the response to natural infection. Immune transfer to neonates occurred via placental and breastmilk.

Background Both T cell activation during early HIV-1 infection and soluble markers of immune activation during chronic infection are predictive of HIV disease progression. Although the acute phase of HIV infection is associated with increased pro-inflammatory cytokine production, the relationship between cytokine concentrations and HIV pathogenesis is unknown. Objectives To identify cytokine biomarkers measurable in plasma during acute HIV-1 infection that predict HIV disease progression. Design Study including 40 South African women who became infected with HIV-1 and were followed longitudinally from the time of infection. Methods The concentrations of 30 cytokines in plasma from women with acute HIV-1 infection were measured and associations between cytokine levels and both viral load set-point 12 months post-infection and time taken for CD4 counts to fall below 350 cells/μl were determined using multivariate and Cox proportional-hazards regression. Results We found that the concentrations of 5 plasma cytokines, IL-12p40, IL-12p70, IFN-γ, IL-7 and IL-15, in women with acute infection predicted 66% of the variation in viral load set-point 12 months post infection. IL-12p40, IL-12p70 and IFN-γ were significantly associated with lower viral load whereas IL-7 and IL-15 were associated with higher viral load. Plasma concentrations of IL-12p40 and GM-CSF during acute infection were associated with maintenance of CD4 counts above 350 cells/μl while IL-1α, eotaxin and IL-7 were associated with more rapid CD4 loss. Conclusions A small panel of plasma cytokines during acute HIV-1 infection was predictive of long-term HIV disease prognosis in this group of South African women.

Antibiotic resistance is a global crisis driven by appropriate and inappropriate antibiotic use to treat human illness and promote animal growth. The antimicrobial resistance epidemic continues to spread due to the triple threat of unfettered access, minimal product regulation and oversight of antibiotic prescription, and lack of clinical diagnostic tools to support antibiotic de-escalation in low-resource settings. In high-resource settings, evidence-based strategies have improved appropriateness of antibiotic use, limiting the spread of drug-resistant organisms and reducing hospital-associated infections, which may also be effective to stop the spread of resistance in resource-poor countries. Current research and surveillance efforts on antimicrobial resistance and hospital-associated infections in low-resource settings are extremely limited, largely focused intensive care units. Many challenges exist to improving antibiotic use and infection control in resource-limited settings, and turning the tide requires intensifying research and surveillance, antimicrobial stewardship, and developing new bedside diagnostic tools for bacterial infections and antimicrobial susceptibility.

Based on the high PPV and NPV, HRP2-based RDTs are likely to be the best diagnostic choice for areas with medium-to-high malaria transmission rates in Africa.

Background Real-time PCR is recommended to detect SARS-CoV-2 infection. However, PCR availability is restricted in most countries. Rapid diagnostic tests are considered acceptable alternatives, but data are lacking on their performance. We assessed the performance of four antibody-based rapid diagnostic tests and one antigen-based rapid diagnostic test for detecting SARS-CoV-2 infection in the community in Cameroon. MethodsIn this clinical, prospective, diagnostic accuracy study, we enrolled individuals aged at least 21 years who were either symptomatic and suspected of having COVID-19 or asymptomatic and presented for screening. We tested peripheral blood for SARS-CoV-2 antibodies using the Innovita (Biological Technology; Beijing, China), Wondfo (Guangzhou Wondfo Biotech; Guangzhou, China), SD Biosensor (SD Biosensor; Gyeonggi-do, South Korea), and Runkun tests (Runkun Pharmaceutical; Hunan, China), and nasopharyngeal swabs for SARS-CoV-2 antigen using the SD Biosensor test. Antigen rapid diagnostic tests were compared with Abbott PCR testing (Abbott; Abbott Park, IL, USA), and antibody rapid diagnostic tests were compared with Biomerieux immunoassays (Biomerieux; Marcy l'Etoile, France). We retrospectively tested two diagnostic algorithms that incorporated rapid diagnostic tests for symptomatic and asymptomatic patients using simulation modelling. Findings 1195 participants were enrolled in the study. 347 (29%) tested SARS-CoV-2 PCR-positive, 223 (19%) rapid diagnostic test antigen-positive, and 478 (40%) rapid diagnostic test antibody-positive. Antigen-based rapid diagnostic test sensitivity was 80•0% (95% CI 71•0-88•0) in the first 7 days after symptom onset, but antibody-based rapid diagnostic tests had only 26•8% sensitivity (18•3-36•8). Antibody rapid diagnostic test sensitivity increased to 76•4% (70•1-82•0) 14 days after symptom onset. Among asymptomatic participants, the sensitivity of antigen-based and antibody-based rapid diagnostic tests were 37•0% (27•0-48•0) and 50•7% (42•2-59•1), respectively. Cohen's κ showed substantial agreement between Wondfo antibody rapid diagnostic test and gold-standard ELISA (κ=0•76; sensitivity 0•98) and between Biosensor and ELISA (κ=0•60; sensitivity 0•94). Innovita (κ=0•47; sensitivity 0•93) and Runkun (κ=0•43; sensitivity 0•76) showed moderate agreement. An antigen-based retrospective algorithm applied to symptomatic patients showed 94•0% sensitivity and 91•0% specificity in the first 7 days after symptom onset. For asymptomatic participants, the algorithm showed a sensitivity of 34% (95% CI 23•0-44•0) and a specificity of 92•0% (88•0-96•0). Interpretation Rapid diagnostic tests had good overall sensitivity for diagnosing SARS-CoV-2 infection. Rapid diagnostic tests could be incorporated into efficient testing algorithms as an alternative to PCR to decrease diagnostic delays and onward viral transmission. Funding Médecins Sans Frontières WACA and Médecins Sans Frontières OCG.

Inflammatory responses at mucosal surfaces after human immunodeficiency virus type 1 (HIV-1) transmission may influence disease outcome. We evaluated levels of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha, IL-8, IL-10, and IL-12 in genital tract and plasma specimens from 44 women with acute HIV infection and 29 HIV-negative control women (13 of whom were women in the acute HIV infection cohort who had preinfection samples available for analysis). Women with acute HIV infection had significantly elevated levels of IL-6, IL-10, and IL-12 in genital tract specimens and elevated levels of IL-1beta, IL-8, and IL-10 in plasma specimens, compared with HIV-negative control women. Levels of IL-1beta, IL-6, and IL-8 in cervicovaginal specimens from women with acute HIV infection showed a significant inverse correlation with systemic CD4(+) cell counts, suggesting that mucosal inflammation is associated with low CD4(+) cell counts during acute HIV infection.