Monkeypox in human pregnancy: an overview.

Monkeypox is a viral zoonosis caused by the monkeypox virus, an enveloped, double-stranded DNA virus belonging to the Orthopoxvirus genus in the Poxviridae family. Monkeypox has become a disease of global public health significance. Pregnant women are unfortunately among the those at an increased risk for exposure to monkeypox because their immune system is altered during pregnancy. They may also be at risk for more severe disease or a worse outcome than others. During pregnancy or while breastfeeding when consideration is given for pre-exposure or postexposure vaccination, nonreplicating (Modivied Vaccinia Ankara - Bavarian Nordic) or minimally replicating (LC16, KM Biologics) vaccines are preferred. The ACAM2000 vaccine is contraindicated in pregnancy because it contains live virus particles that can cause fetal vaccinia and fetal death. There are no data to support the use of tecovirimat in pregnant women. However, no fetal adverse effects were noticed when tecovirimat was used in animal studies.

Hydroxyurea for primary stroke prevention in children with sickle cell anaemia in Nigeria (SPRING): a double-blind, multicentre, randomised, phase 3 trial.

BACKGROUND: In high-income countries, standard care for primary stroke prevention in children with sickle cell anaemia and abnormal transcranial Doppler velocities results in a 92% relative risk reduction of strokes but mandates initial monthly blood transfusion. In Africa, where regular blood transfusion is not feasible for most children, we tested the hypothesis that initial moderate-dose compared with low-dose hydroxyurea decreases the incidence of strokes for children with abnormal transcranial Doppler velocities. METHODS: SPRING is a double-blind, parallel-group, randomised, controlled, phase 3 trial of children aged 5-12 years with sickle cell anaemia with abnormal transcranial Doppler velocities conducted at three teaching hospitals in Nigeria. For randomisation, we used a permuted block allocation scheme with block sizes of four, stratified by sex and site. Allocation was concealed from all but the pharmacists and statisticians. Participants were assigned in a 1:1 ratio to low-dose (10 mg/kg per day) or moderate-dose (20 mg/kg per day) oral hydroxyurea taken once daily with monthly clinical evaluation and laboratory monitoring. The primary outcome was initial stroke or transient ischaemic attack, centrally adjudicated. The secondary outcome was all-cause hospitalisation. We used the intention-to-treat population for data analysis. The trial was stopped early for futility after a planned minimum follow-up of 3·0 years to follow-up for participants. This trial was registered with ClinicalTrials.gov, number NCT02560935. FINDINGS: Between Aug 2, 2016, and June 14, 2018, 220 participants (median age 7·2 years [IQR 5·5-8·9]; 114 [52%] female) were randomly allocated and followed for a median of 2·4 years (IQR 2·0-2·8). All participants were Nigerian and were from the following ethnic groups: 179 (82%) people were Hausa, 25 (11%) were Fulani, and 16 (7%) identified as another ethnicity. In the low-dose hydroxyurea group, three (3%) of 109 participants had strokes, with an incidence rate of 1·19 per 100 person-years and in the moderate-dose hydroxyurea group five (5%) of 111 had strokes with an incidence rate of 1·92 per 100 person-years (incidence rate ratio 0·62 [95% CI 0·10-3·20], p=0·77). The incidence rate ratio of hospitalisation for any reason was 1·71 (95% CI 1·15-2·57, p=0·0071), with higher incidence rates per 100 person-years in the low-dose group versus the moderate-dose group (27·43 vs 16·08). No participant had hydroxyurea treatment stopped for myelosuppression. INTERPRETATION: Compared with low-dose hydroxyurea therapy, participants treated with moderate-dose hydroxyurea had no difference in the stroke incidence rate. However, secondary analyses suggest that the moderate-dose group could lower incidence rates for all-cause hospitalisations. These findings provide an evidence-based guideline for the use of low-dose hydroxyurea therapy for children with sickle cell anaemia at risk of stroke. FUNDING: National Institute of Neurological Disorders and Stroke.

High Systolic Blood Pressure, Anterior Segment Changes and Visual Impairment Independently Predict Sickle Cell Retinopathy.

Sickle cell disease is often complicated by retinopathy, which can be proliferative or non proliferative. Proliferative sickle cell retinopathy potentially leads to blindness. There is a paucity of data on sickle cell disease-related retinopathy from Africa, where the disease is most prevalent. We aimed to determine the clinical, ophthalmic, and laboratory predictors of sickle cell retinopathy in an African population. We conducted a cross-sectional study of 262 participants, aged 13 years and above, with sickle cell disease. Demographic and clinical data were collected using a structured questionnaire and standard physical examinations. Vitreo-retinal specialists performed eye examinations on all the participants. Hematological and biochemical assessments were conducted using standard methods. A multivariate stepwise forward logistic regression was performed to determine the predictors of retinopathy. The median age of the participants was 20 years (interquartile range: 17-25 years). Most of the participants had a homozygous Hb S (HBB: c.20A>T) genotype (96.9%), with 3.1% who carried a Hb S/Hb C (HBB: c.19G>A) genotype. The prevalence of non proliferative sickle cell retinopathy was 24.4%. Only 1.9% had proliferative sickle cell retinopathy (PSCR). Elevated systolic blood pressure (BP) [odds ratio (OR): 6.85, 95% confidence interval (95% CI): 1.05-44.45, p = 0.059], moderate visual impairment (OR: 5.2, 95% CI: 1.39-19.63, p = 0.015), and anterior segment changes (OR: 2.21, 95% CI: 1.19-4.13, p = 0.012) were independently predictive of retinopathy. This study provides new insight into predictors of retinopathy in sickle cell disease, with implications on early screening and prevention.

"A child with sickle cell disease can't live with just anyone." A mixed methods study of socio-behavioral influences and severity of sickle cell disease in northern Nigeria.

BACKGROUND: The modulatory effects of psychosocial and biophysical environments on sickle cell disease (SCD) severity during childhood has not been well characterized in high burden settings, such as Nigeria. OBJECTIVES: We identified socio-demographic correlates and explored caregivers' perceptions on socio-behavioral and environmental influences on hospitalization for pain and blood transfusion of children with SCD in Kano, Nigeria. METHODS: Using mixed methods, structured questionnaires were administered to a clinic-based sample of caregivers of children with SCD (n = 372), complemented with eight focus group discussions. Binary logistic regression models and the framework approach were used to analyze the data. RESULTS: The majority (73.1%, n = 272) of the children had at least one vaso-occlusive crisis (VOC), and 41.1% (n = 153) required hospitalization in the preceding year. A total of 170 children (45.7%) received blood transfusion. Hospitalization was predicted by the child's age (Adjusted Odds Ratio, AOR = 1.89; 95% Confidence Interval, CI: 1.18-4.07, ≥10 vs <5 years), relationship with caregiver (AOR = 5.41; 95%CI: 1.17-25.05, mother vs "others"), father's number of children (AOR = 2.21; 95%CI: 1.19-5.31, ≥10 vs ≤4), and siblings with SCD (AOR = 2.36; 95%CI: 1.16-8.80, 2 vs 0). Caregivers perceived maternal care, stable home environment, medication adherence, anti-mosquito measures, and adequate nutrition as protective factors, whereas poverty, extreme emotions, physical exertion, and extreme temperatures were identified as detrimental to the health of the child. CONCLUSIONS: Hospitalizations for VOC and transfusion rates among children with SCD were high. Understanding the modulatory effects of socio-behavioral factors on SCD severity could inform preventive measures and enhance the quality of life of affected children.

Primary prevention of stroke in children with sickle cell anemia in sub-Saharan Africa: rationale and design of phase III randomized clinical trial.

Strokes in children with sickle cell anemia (SCA) are associated with significant morbidity and premature death. Primary stroke prevention in children with SCA involves screening for abnormal transcranial Doppler (TCD) velocity coupled with regular blood transfusion therapy for children with abnormal velocities, for at least one year. However, in Africa, where the majority of children with SCA live, regular blood transfusions are not feasible due to inadequate supply of safe blood, cost, and the reluctance of caregivers to accept transfusion therapy for their children. We describe the Primary Prevention of Stroke in Children with Sickle Cell Disease in Nigeria Trial [StrokePreventioninNigeria (SPRING) trial, NCT02560935], a three-center double-blinded randomized controlled Phase III clinical trial to 1) determine the efficacy of moderate fixed-dose (20 mg/kg/day) versus low fixed-dose (10 mg/kg/day) hydroxyurea therapy for primary stroke prevention; 2) determine the efficacy of moderate fixed-dose hydroxyurea for decreasing the incidence of all cause-hospitalization (pain, acute chest syndrome, infection, other) compared to low fixed-dose hydroxyurea. We will test the primary hypothesis that there will be a 66% relative risk reduction of strokes in children with SCA and abnormal TCD measurements, randomly allocated, for a minimum of three years to receive moderate fixed-dose versus low fixed-dose hydroxyurea (total n = 220). The results of this trial will advance the care of children with SCA in sub-Saharan Africa, while improving research capacity for future studies to prevent strokes in children with SCA.