Association between HIV Serostatus and premalignant cervical lesions among women attending a cervical cancer screening clinic at a tertiary care facility in southwestern Uganda: a comparative cross-sectional study.

BACKGROUND: Uganda has approximately 1.2 million people aged 15-64 years living with human immunodeficiency virus (HIV). Previous studies have shown a higher prevalence of premalignant cervical lesions among HIV-positive women than among HIV-negative women. Additionally, HIV-infected women are more likely to have human papilloma virus (HPV) infection progress to cancer than women not infected with HIV. We determined the prevalence of premalignant cervical lesions and their association with HIV infection among women attending a cervical cancer screening clinic at Mbarara Regional Referral Hospital (MRRH) in southwestern Uganda. METHODS: We conducted a comparative cross-sectional study of 210 women aged 22-65 years living with HIV and 210 women not living with HIV who were systematically enrolled from March 2022 to May 2022. Participants were subjected to a structured interviewer-administered questionnaire to obtain their demographic and clinical data. Additionally, Papanicolaou smears were obtained for microscopy to observe premalignant cervical lesions. Multivariate logistic regression was performed to determine the association between HIV status and premalignant cervical lesions. RESULTS: The overall prevalence of premalignant cervical lesions in the study population was 17% (n = 72; 95% C.I: 14.1-21.4), with 23% (n = 47; 95% C.I: 17.8-29.5) in women living with HIV and 12% (n = 25; 95% C.I: 8.2-17.1) in women not living with HIV (p < 0.003). The most common premalignant cervical lesions identified were low-grade squamous intraepithelial lesions (LSIL) in both women living with HIV (74.5%; n = 35) and women not living with HIV (80%; n = 20). HIV infection was significantly associated with premalignant lesions (aOR: 2.37, 95% CI: 1.27-4.42; p = 0.007). CONCLUSION: Premalignant cervical lesions, particularly LSILs, were more common in HIV-positive women than in HIV-negative women, highlighting the need to strengthen the integration of cervical cancer prevention strategies into HIV care programs.

Abnormal obstetric shock index and associated factors among immediate postpartum women following vaginal delivery at a tertiary hospital in southwestern Uganda.

BACKGROUND: Early recognition of haemodynamic instability after birth and prompt interventions are necessary to reduce adverse maternal outcomes due to postpartum haemorrhage. Obstetric shock Index (OSI) has been recommended as a simple, accurate, reliable, and low-cost early diagnostic measure that identifies hemodynamically unstable women. OBJECTIVES: We determined the prevalence of abnormal obstetric shock index and associated factors among women in the immediate postpartum period following vaginal delivery at Mbarara Regional Referral Hospital (MRRH) in southwestern Uganda. METHODS: We conducted a cross-sectional study at the labour suite and postnatal ward of MRRH from January 2022 to April 2022. We systematically sampled women who had delivered vaginally, and measured their blood pressures and pulse rates at 1 h postpartum. We excluded mothers with hypertensive disorders of pregnancy. Sociodemographic, medical and obstetric data were obtained through interviewer-administered questionnaires. The prevalence of abnormal OSI was the proportion of participants with an OSI ≥ 0.9 (calculated as the pulse rate divided by the systolic BP). Logistic regression analysis was used to determine associations between abnormal OSI and independent variables. RESULTS: We enrolled 427 women with a mean age of 25.66 ± 5.30 years. Of these, 83 (19.44%), 95% CI (15.79-23.52) had an abnormal obstetric shock index. Being referred [aPR 1.94, 95% CI (1.31-2.88), p = 0.001], having had antepartum haemorrhage [aPR 2.63, 95% CI (1.26-5.73), p = 0.010] and having a visually estimated blood loss > 200 mls [aPR 1.59, 95% CI (1.08-2.33), p = 0.018] were significantly associated with abnormal OSI. CONCLUSION: Approximately one in every five women who delivered vaginally at MRRH during the study period had an abnormal OSI. We recommend that clinicians have a high index of suspicion for haemodynamic instability among women in the immediate postpartum period. Mothers who are referred in from other facilities, those that get antepartum haemorrhage and those with estimated blood loss > 200mls should be prioritized for close monitoring. It should be noted that the study was not powered to study the factors associated with AOSI and therefore the analysis for factors associated should be considered exploratory.

Maternal near miss as a predictor of adverse perinatal outcomes: findings from a prospective cohort study in southwestern Uganda.

BACKGROUND: Despite efforts, Uganda has not met the World Health Organization target of < 12 newborn deaths per 1,000 live births. Severe maternal morbidity or 'near miss' is a major contributor to adverse perinatal outcomes, particularly in low-resource settings. However, the specific impact of maternal near miss on perinatal outcomes in Uganda remains insufficiently investigated. We examined the association between maternal near miss and adverse perinatal outcomes at Mbarara Regional Referral Hospital (MRRH) in southwestern Uganda. METHODS: We conducted a prospective cohort study among women admitted for delivery at MRRH's maternity ward from April 2022 to August 2022. We included mothers at ≥ 28 weeks of gestation with singleton pregnancies, while intrauterine fetal death cases were excluded. For the near-miss group, we consecutively included mothers with any one of the following: antepartum hemorrhage with shock, uterine rupture, hypertensive disorders, coma, and cardiac arrest; those without these complications constituted the non-near-miss group. We followed the mothers until delivery, and their infants until seven days postpartum or death. Adverse perinatal outcomes considered were low birth weight (< 2,500 g), low Apgar score (< 7 at five minutes), intrapartum stillbirths, early neonatal death, or admission to neonatal intensive care unit. Multivariable log-binomial regression was used to determine predictors of adverse perinatal outcomes. RESULTS: We enrolled 220 participants (55 maternal near misses and 165 non-near misses) with a mean age of 27 ± 5.8 years. Most of the near misses were pregnancies with hypertensive disorders (49%). Maternal near misses had a four-fold (adjusted risk ratio [aRR] = 4.02, 95% CI: 2.32-6.98) increased risk of adverse perinatal outcomes compared to non-near misses. Other predictors of adverse perinatal outcomes were primigravidity (aRR = 1.53, 95%CI: 1.01-2.31), and gestational age < 34 weeks (aRR = 1.81, 95%CI: 1.19-2.77). CONCLUSION: Maternal near misses, primigravidity, and preterm pregnancies were independent predictors of adverse perinatal outcomes in this study. We recommend implementing maternal near-miss surveillance as an integral component of comprehensive perinatal care protocols, to improve perinatal outcomes in Uganda and similar low-resource settings. Targeted interventions, including specialized care for women with maternal near misses, particularly primigravidas and those with preterm pregnancies, could mitigate the burden of adverse perinatal outcomes.

Spike protein is a key target for stronger and more persistent T-cell responses-a study of mild and asymptomatic SARS-CoV-2 infection.

OBJECTIVES: Understanding the immune response in very mild and asymptomatic COVID-19 is crucial for developing effective vaccines and immunotherapies, yet remains poorly characterized. This longitudinal study examined the evolution of interferon (IFN)-γ responses to SARS-CoV-2 peptides in 109 asymptomatic or mildly symptomatic Ugandan COVID-19 patients across 365 days and explored their association with antibody generation. METHODS: T-cell responses to spike-containing clusters of differentiation (CD4)-S and CD8 nCoV-A (CD8-A) megapools, and the non-spike CD4-R and CD8 nCoV-B (CD8-B) megapools, were assessed and correlated with demographic and temporal variables. RESULTS: SARS-CoV-2-specific IFN-γ responses were consistently detected in all peptide pools and time points, with the spike-targeted response exhibiting higher potency and durability than the non-spike responses. Throughout the entire 365-day infection timeline, a robust positive correlation was observed between CD4 T-cell responses to the spike-derived peptides and anti-spike immunoglobulin G antibody levels, underscoring their interdependent dynamics in the immune response against SARS-CoV-2; in contrast, CD8 T-cell responses exhibited no such correlation, highlighting their distinctive, autonomous role in defense. No meaningful variations in complete blood count parameters were observed between individuals with COVID-19 infection and those without, indicating clinical insignificance. CONCLUSIONS: This study highlights the dominant role of spike-directed T-cell responses in mild and asymptomatic disease and provides crucial longitudinal data from Sub-Saharan African settings. The findings provide valuable insights into the dynamics of T-cell responses and their potential significance in developing effective strategies for combating COVID-19.

Rapid, early, and potent Spike-directed IgG, IgM, and IgA distinguish asymptomatic from mildly symptomatic COVID-19 in Uganda, with IgG persisting for 28 months.

Introduction: Understanding how spike (S)-, nucleoprotein (N)-, and RBD-directed antibody responses evolved in mild and asymptomatic COVID-19 in Africa and their interactions with SARS-CoV-2 might inform development of targeted treatments and vaccines. Methods: Here, we used a validated indirect in-house ELISA to characterise development and persistence of S- and N-directed IgG, IgM, and IgA antibody responses for 2430 SARS-CoV-2 rt-PCR-diagnosed Ugandan specimens from 320 mild and asymptomatic COVID-19 cases, 50 uninfected contacts, and 54 uninfected non-contacts collected weekly for one month, then monthly for 28 months. Results: During acute infection, asymptomatic patients mounted a faster and more robust spike-directed IgG, IgM, and IgA response than those with mild symptoms (Wilcoxon rank test, p-values 0.046, 0.053, and 0.057); this was more pronounced in males than females. Spike IgG antibodies peaked between 25 and 37 days (86.46; IQR 29.47-242.56 BAU/ml), were significantly higher and more durable than N- and RBD IgG antibodies and lasted for 28 months. Anti-spike seroconversion rates consistently exceeded RBD and nucleoprotein rates. Spike- and RBD-directed IgG antibodies were positively correlated until 14 months (Spearman's rank correlation test, p-values 0.0001 to 0.05), although RBD diminished faster. Significant anti-spike immunity persisted without RBD. 64% and 59% of PCR-negative, non-infected non-contacts and suspects, exhibited baseline SARS-CoV-2 N-IgM serological cross-reactivity, suggesting undetected exposure or abortive infection. N-IgG levels waned after 787 days, while N-IgM levels remained undetectable throughout. Discussion: Lower N-IgG seroconversion rates and the absence of N-IgM indicate that these markers substantially underestimate the prior exposure rates. Our findings provide insights into the development of S-directed antibody responses in mild and asymptomatic infections, with varying degrees of symptoms eliciting distinct immune responses, suggesting distinct pathogenic pathways. These longer-lasting data inform vaccine design, boosting strategies, and surveillance efforts in this and comparable settings.