Maternal COVID-19 infection and associated factors: A cross-sectional study.

BACKGROUND: Since the declaration of COVID-19 as a global pandemic, several studies have been conducted to examine associated factors. However, few studies have focused on pregnant women infected with COVID-19 in sub-Saharan Africa. Therefore, this study investigated the prevalence and factors associated with COVID-19 infection among pregnant women at the Levy Mwanawasa University Teaching Hospital and Women and Newborn Hospital of the University Teaching Hospitals in Lusaka, Zambia. METHODS: A cross-sectional study was conducted between March and July 2021. Women were recruited as they presented for antenatal care. Data was collected using a structured questionnaire to capture variables of interest (socio-demographic, clinical and obstetric). COVID-19 diagnosis was made using a nasopharyngeal swab by PCR test. Multivariable logistic regression was used to control for confounding and calculate the odds ratios for each explanatory variable and respective 95% confidence intervals. RESULTS: The study enrolled 352 participants with a mean (standard deviation [SD]) age of 30.1 years (5.6). One hundred thirty of 352 (36.9%; 95% CI: 31.9 to 42.2) participants had a confirmed positive SARS-CoV-2 test result. At univariable analysis, factors associated with COVID-19 were increased gestational age, education status and maternal HIV serostatus. Women with a secondary level of education were less likely to have COVID-19 infection than those with a primary level of education (AOR = 0.23, 95% CI: 0.09-0.63). On the other hand, a one-week increase in gestational age was associated with higher odds of COVID-19 infection (AOR = 1.03, 95% CI: 1.01-1.06). CONCLUSION: The results showed that the prevalence of COVID-19 infection among pregnant women was 36.9% and was associated with increased gestational age and a lower level of education. To mitigate adverse maternal outcomes, there is a need to screen for COVID-19 strictly and broadly monitor prenatal women presenting for healthcare.

Knowledge, Attitudes and Practices Towards Human Papillomavirus Vaccination Among Medical Doctors at a Tertiary Hospital: A Cross Sectional Study.

BACKGROUND: Human papillomavirus (HPV) infection is a common sexually transmitted disease, characterised by persistent infection with high-risk strains leading to malignant conditions such as cervical cancer. The HPV vaccine is a well-known primary preventive measure for HPV infections. Previous studies have shown that medical doctors' vaccine recommendation is one of the key strategies in improving HPV vaccine uptake. In 2019, Zambia rolled out the free national HPV vaccination program targeting 14-year-old girls. However, the annual coverage for HPV vaccination is variable, with rates as low as 33% for 2021. MATERIALS AND METHODS: We conducted a cross-sectional study between September and December 2020 at the University Teaching Hospitals in Lusaka, Zambia. We used analysis of variance to assess the mean differences in the overall scores for knowledge, attitude and practices towards the HPV vaccine. In addition, we used structural equation modelling (SEM) to test the traditional education theory as medical doctors' HPV vaccine knowledge, attitude, and practices cover several facets, and SEM can model latent variables. RESULTS: We enrolled 121 medical doctors, of whom 67 (44.6%) were male. The majority, 76 (62.8%), were registrars and 79 (65.3%) had more than ten years of clinical experience. The overall mean knowledge, attitude, and practice score of the HPV vaccine mean (SD) were 70.2 (15.1), 72.1 (18.5) and 77.1 (28.9), respectively. More than half of the medical doctors would advise anyone eligible to take the HPV vaccine 66 (54.6%). There was a positive correlation between attitude and practice towards the HPV vaccine (ß = .03, P = .017). Conversely, there was no evidence of a correlation between overall HPV knowledge and attitude (ß = .01, P = .670) and rank of the medical doctors (ß = -7.87, P = .355). CONCLUSION: Knowledge was high with good attitudes and practices among medical doctors, which are vital in vaccine recommendation and subsequent uptake.

Psychosocial issues and coping mechanisms of pregnant and postnatal women diagnosed with COVID-19: A qualitative study.

OBJECTIVE: There is a paucity of data on the psychosocial issues and coping mechanisms among pregnant and postnatal women with COVID-19 infection. We, therefore, aimed to explore the psychosocial issues and coping mechanisms of pregnant and postnatal women diagnosed with COVID-19 at tertiary-level hospitals. METHODS: This was a qualitative phenomenological study conducted in 2021 with a sample size of 16 women admitted at two referral hospitals serving as COVID-19 admission facilities for pregnant and postnatal women in Lusaka, Zambia. In-depth interviews were conducted via telephone to understand what these women experienced when diagnosed with COVID-19. All the interviews were audio-recorded and transcribed verbatim. Thematic analysis was conducted using the six steps approach to develop emerging themes. RESULTS: Two major themes emerged: psychosocial issues and coping mechanisms. The primary psychosocial issues were worry and stigma. Women worried about infecting their unborn baby or neonate, being separated from the baby, the general safety of the baby, and the health of other family members. Women also worried about the attitude of health care providers and faced discrimination or stigma because of their infection. Thus, some coping mechanisms were developed that helped them, such as a positive attitude, keeping the disease secret, reliance on family members for support and using positive information from social media. CONCLUSION: This study provides unique insights into the psychosocial experiences of pregnant and postnatal women diagnosed with COVID-19. Women were particularly concerned about the unborn baby's well-being and discrimination.This study suggests the need for policy and clinical practice to consider the integration of effective mental health services into the provision of maternal health and COVID-19 services.

Perinatal hypoxia aggravates occlusive pulmonary vasculopathy in SU5416/hypoxia-treated rats later in life.

Pulmonary arterial hypertension (PAH) is a fatal disease, which is characterized by occlusive pulmonary vascular disease (PVD) in small pulmonary arteries. It remains unknown whether perinatal insults aggravate occlusive PVD later in life. We tested the hypothesis that perinatal hypoxia aggravates PVD and survival in rats. PVD was induced in rats with/without perinatal hypoxia (embryonic day 14 to postnatal day 3) by injecting SU5416 at 7 wk of age and subsequent exposure to hypoxia for 3 wk (SU5416/hypoxia). Hemodynamic and morphological analyses were performed in rats with/without perinatal hypoxia at 7 wk of age (baseline rats, n = 12) and at 15 wk of age in 4 groups of rats: SU5416/hypoxia or control rats with/without perinatal hypoxia (n = 40). Pulmonary artery smooth muscle cells (PASMCs) from the baseline rats with/without perinatal hypoxia were used to assess cell proliferation, inflammation, and genomic DNA methylation profile. Although perinatal hypoxia alone did not affect survival, physiological, or pathological parameters at baseline or at the end of the experimental period in controls, perinatal hypoxia decreased weight gain and survival rate and increased right ventricular systolic pressure, right ventricular hypertrophy, and indices of PVD in SU5416/hypoxia rats. Perinatal hypoxia alone accelerated the proliferation and inflammation of cultured PASMCs from baseline rats, which was associated with DNA methylation. In conclusion, we established the first fatal animal model of PAH with worsening hemodynamics and occlusive PVD elicited by perinatal hypoxia, which was associated with hyperproliferative, proinflammatory, and epigenetic changes in cultured PASMCs. These findings provide insights into the treatment and prevention of occlusive PVD.

CRISPR-mediated Bmpr2 point mutation exacerbates late pulmonary vasculopathy and reduces survival in rats with experimental pulmonary hypertension.

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) carrying bone morphogenetic protein receptor type 2 (Bmpr2) mutations present earlier with severe hemodynamic compromise and have poorer survival outcomes than those without mutation. The mechanism underlying the worsening clinical phenotype of PAH with Bmpr2 mutations has been largely unaddressed in rat models of pulmonary hypertension (PH) because of the difficulty in reproducing progressive PH in mice and genetic modification in rats. We tested whether a clinically-relevant Bmpr2 mutation affects the progressive features of monocrotaline (MCT) induced-PH in rats. METHODS: A monoallelic single nucleotide insertion in exon 1 of Bmpr2 (+/44insG) was generated in rats using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9, then PH, pulmonary vascular disease (PVD) and survival after MCT injection with or without a phosphodiesterase type 5 inhibitor, tadalafil, administration were assessed. RESULTS: The +/44insG rats had reduced BMPR2 signalling in the lungs compared with wild-type. PH and PVD assessed at 3-weeks after MCT injection were similar in wild-type and +/44insG rats. However, survival at 4-weeks after MCT injection was significantly reduced in +/44insG rats. Among the rats surviving at 4-weeks after MCT administration, +/44insG rats had increased weight ratio of right ventricle to left ventricle plus septum (RV/[LV + S]) and % medial wall thickness (MWT) in pulmonary arteries (PAs). Immunohistochemical analysis showed increased vessels with Ki67-positive cells in the lungs, decreased mature and increased immature smooth muscle cell phenotype markers in the PAs in +/44insG rats compared with wild-type at 3-weeks after MCT injection. Contraction of PA in response to prostaglandin-F2α and endothelin-1 were significantly reduced in the +/44insG rats. The +/44insG rats that had received tadalafil had a worse survival with a significant increase in RV/(LV + S), %MWT in distal PAs and RV myocardial fibrosis compared with wild-type. CONCLUSIONS: The present study demonstrates that the Bmpr2 mutation promotes dedifferentiation of PA smooth muscle cells, late PVD and RV myocardial fibrosis and adversely impacts both the natural and post-treatment courses of MCT-PH in rats with significant effects only in the late stages and warrants preclinical studies using this new genetic model to optimize treatment outcomes of heritable PAH.

Lung damage created by high tidal volume ventilation in rats with monocrotaline-induced pulmonary hypertension.

BACKGROUND: Rats with chronic hypoxia-induced non-inflammatory pulmonary hypertension (PH) are resistant to ventilator-induced lung injury. We investigated the effect of high tidal volume ventilation in another model of PH, monocrotaline (MCT)-induced PH, which is a type of inflammatory PH. METHODS: PH was induced in rats by subcutaneous injection with 60 mg/kg MCT. Normal control rats, rats at 2 weeks after MCT injection (MCT2), and rats at 3 weeks after MCT injection (MCT3) were ventilated with low tidal volume (LV, 6 mL/kg) or high tidal volume (HV, 35 mL/kg) for 2 h with room air without positive end-expiratory pressure. Arterial oxygen pressure (PaO2) and Evans blue dye (EBD) extravasation were measured. Hypertensive pulmonary vascular remodeling was assessed morphometrically by the percentage of muscularized peripheral pulmonary arteries (%Muscularization) and the media wall thickness to external diameter ratio, namely percentage medial wall thickness (%MWT). To assess inflammation, lung IκB protein and cytokine mRNA expression levels were assessed. RESULTS: Baseline mean pulmonary arterial pressure was significantly higher in MCT rats (normal, 15.4 ± 0.5 mmHg; MCT2, 23.7 ± 0.9; and MCT3, 34.5 ± 1.5). After 2-h ventilation, PaO2 was significantly lower in the HV groups compared with the LV groups in normal and MCT2 rats, but not in MCT3 rats. Impairment of oxygenation with HV was less in MCT3 rats compared with normal and MCT2 rats. Among the HV groups, MCT3 rats showed significantly lower levels of EBD extravasation than normal and MCT2 rats. HV significantly downregulated IκB protein expression in normal and MCT3 rats and increased IL-6, MCP-1, CXCL-1 (MIP-1), and IL-10 mRNA levels in MCT3 rats. %Muscularization, %MWT, and the expression of lung elastin were significantly higher in MCT3 rats than in normal and MCT2 rats. CONCLUSION: We found that HV-associated damage might be reduced in MCT-induced PH rats compared with normal rats. The results of this and earlier studies suggest that hypertensive pulmonary vascular structural changes might be protective against the occurrence of ventilator-induced lung injury, irrespective of the etiology of PH.

Model difference in the effect of cilostazol on the development of experimental pulmonary hypertension in rats.

BACKGROUND: Preventing pulmonary vascular remodeling is a key strategy for pulmonary hypertension (PH). Causes of PH include pulmonary vasoconstriction and inflammation. This study aimed to determine whether cilostazol (CLZ), a phosphodiesterase-3 inhibitor, prevents monocrotaline (MCT)- and chronic hypoxia (CH)-induced PH development in rats. METHODS: Fifty-one male Sprague-Dawley rats were fed rat chow with (0.3% CLZ) or without CLZ for 21 days after a single injection of MCT (60 mg/kg) or saline. Forty-eight rats were fed rat chow with and without CLZ for 14 days under ambient or hypobaric (air at 380 mmHg) CH exposure. The mean pulmonary artery pressure (mPAP), the right ventricle weight-to-left ventricle + septum weight ratio (RV/LV + S), percentages of muscularized peripheral pulmonary arteries (%Muscularization) and medial wall thickness of small muscular arteries (%MWT) were assessed. Levels of the endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (peNOS), AKT, pAKT and IκB proteins in lung tissue were measured using Western blotting. Monocyte chemotactic protein (MCP)-1 mRNA in lung tissue was also assessed. RESULTS: mPAP [35.1 ± 1.7 mmHg (MCT) (n = 9) vs. 16.6 ± 0.7 (control) (n = 9) (P < 0.05); 29.1 ± 1.5 mmHg (CH) (n = 10) vs. 17.5 ± 0.5 (control) (n = 10) (P < 0.05)], RV/LV + S [0.40 ± 0.01 (MCT) (n = 18) vs. 0.24 ± 0.01 (control) (n = 10) (P < 0.05); 0.41 ± 0.03 (CH) (n = 13) vs. 0.27 ± 0.06 (control) (n = 10) (P < 0.05)], and %Muscularization and %MWT were increased by MCT injection and CH exposure. CLZ significantly attenuated these changes in the MCT model [mPAP 25.1 ± 1.1 mmHg (n = 11) (P < 0.05), RV/LV + S 0.30 ± 0.01 (n = 14) (P < 0.05)]. In contrast, these CLZ effects were not observed in the CH model. Lung eNOS protein expression was unchanged in the MCT model and increased in the CH model. Lung protein expression of AKT, phosphorylated AKT, and IκB was downregulated by MCT, which was attenuated by CLZ; the CH model did not change these proteins. Lung MCP-1 mRNA levels were increased in MCT rats but not CH rats. CONCLUSIONS: We found model differences in the effect of CLZ on PH development. CLZ might exert a preventive effect on PH development in an inflammatory PH model but not in a vascular structural change model of PH preceded by vasoconstriction. Thus, the preventive effect of CLZ on PH development might depend on the PH etiology.