The brain protection of MLKL inhibitor necrosulfonamide against focal ischemia/reperfusion injury associating with blocking the nucleus and nuclear envelope translocation of MLKL and RIP3K.

Mixed lineage kinase like protein (MLKL) is a key mediator of necroptosis. While previous studies highlighted the important role of MLKL as one of the central regulators of brain damage against acute ischemic neuronal injury, how the activation of MLKL mediates brain injuries and cell death remains unclear, especially in astrocytes. In a transient middle cerebral artery occlusion (tMCAO) rat model in vivo, and an oxygen-glucose deprivation and reoxygenation (OGD/Re) injury model in both primary cultured astrocytes and human astrocytes, we show that necrosulfonamide (NSA), a MLKL specific inhibitor, reduces infarction volume and improves neurological deficits in tMCAO-treated rats. In addition, NSA treatment, as well as RIP1K inhibitor Nec-1 or RIP3K inhibitor GSK-872 treatment, decreases the OGD/Re-induced leakage of LDH in both primary cultured astrocytes and human astrocytes. NSA treatment also reduces the number of propidium iodide (PI)-positive cells, and prevents the upregulation of necroptotic biomarkers such as MLKL/p-MLKL, RIP3K/p-RIP3K, and RIP1K/p-RIP1K in ischemic penumbra of cerebral cortex in tMCAO-treated rats or in OGD/Re-treated human astrocytes. Importantly, NSA treatment blocks both the nucleus and nuclear envelope localization of MLKL/p-MLKL and RIP3K/p-RIP3K in ischemic cerebral cortex induced by tMCAO. Similarly, Co-immunoprecipitation assay shows that NSA treatment decreases tMCAO- or OGD/Re- induced increased combination of MLKL and RIP3K in nuclear envelope of ischemic penumbra of cerebral cortex or of primary cultured astrocytes, respectively. RIP3K inhibitor GSK-872 also reduces tMCAO-induced increased combination of MLKL and RIP3K in nuclear envelope of ischemic penumbra of cerebral cortex. These data suggest NSA exerts protective effects against focal ischemia/reperfusion injury via inhibiting astrocytic necroptosis through preventing the upregulation of necroptotic kinases as well as blocking both the nucleus and nuclear envelope co-localization of p-MLKL and p-RIP3K. The translocation of p-MLKL, along with p-RIP3K, to the nuclear envelope and the nucleus may play a crucial role in MLKL-mediated necroptosis under ischemic conditions.

Evaluation of knowledge, experiences, and fear toward prescribing and dispensing corticosteroids among Egyptian healthcare professionals: A cross-sectional study.

Background: Corticosteroids (CS) are essential drugs in the treatment of several medical conditions. Assuming different roles, physicians and pharmacists play a primary role in prescribing and dispensing these medications to optimize patients' clinical management. The data on assessing knowledge and experience of healthcare professionals toward CS is scarce. Therefore, this study aimed to assess and compare knowledge, experience, and fears towards CS among Egyptian physicians and pharmacists. Methods: A cross-sectional, self-administrated, validated online questionnaire was used to collect the data from Egyptian healthcare professionals. The questionnaire consisted of four sections with multiple choice questions: sociodemographic (7 questions), knowledge about CS (13 questions), experience with CS prescription/dispensing (5 questions), and fears and preferences toward CS prescription/dispensing (13 questions). Descriptive and inferential statistics were used to analyze the data. Results: A total of 600 responses were analyzed in this study. The study sample was almost two-half of healthcare providers: 303 (50.5%) pharmacists and 297 (49.5%) physicians. Pharmacists had marginally higher knowledge scores as compared to those recorded for physicians (11.29 versus 10.16, respectively; P = 0.047). Physicians had more experience choosing corticosteroids in treatment plans based on their experience (51.8% vs 38.5%) and guideline recommendations (72.8% vs 50.9%) than pharmacists. However, pharmacists had more experience dealing with corticosteroid use based on patients' preferences (19.5% vs 4.9%) and showed a broader scope of experiencing side effects of corticosteroids with their patients. The two professions demonstrated high levels of fear, with pharmacists acknowledging significantly lower concerns about CS than physicians (3.72 versus 4.0, respectively; P = 0.003). Conclusion: Discrepancies exist among healthcare professionals in knowledge and experience, favoring better scientific knowledge of pharmacists related to corticosteroids. Based on these findings, the interprofessional collaborative efforts would provide comprehensive, patient-centered care that maximizes the benefits of CS while minimizing their risks.

Understanding Sociodemographic Factors and Reasons Associated with COVID-19 Vaccination Hesitance among Adults in Tanzania: A Mixed-Method Approach.

Although studies on COVID-19 vaccine hesitancy are being undertaken widely worldwide, there is limited evidence in Tanzania. This study aims to assess the sociodemographic factors associated with COVID-19 vaccine hesitancy and the reasons given by unvaccinated study participants. We conducted a mixed-method cross-sectional study with two components-health facilities and communities-between March and September 2022. A structured questionnaire and in-depth interviews were used to collect quantitative and qualitative data, respectively. A total of 1,508 individuals agreed to participate in the survey and explained why they had not vaccinated against COVID-19. Of these participants, 62% indicated they would accept the vaccine, whereas 38% expressed skepticism. In a multivariate regression analysis, adult study participants 40 years and older were significantly more likely to report not intending to be vaccinated (adjusted odds ratio [AOR], 1.28; 95% CI, 1.01-1.61; P = 0.04) than youth and middle-aged study participants between 18 and 40 years. Furthermore, female study participants had a greater likelihood of not intending to be vaccinated (AOR, 1.51; 95% CI, 1.19-1.90; P = 0.001) than male study participants. The study identified fear of safety and short-term side effects, and lack of trust of the COVID-19 vaccine; belief in spiritual or religious views; and belief in local remedies and other precautions or preventive measures as the major contributors to COVID-19 vaccine hesitancy in Tanzania. Further empirical studies are needed to confirm these findings and to understand more fully the reasons for vaccine hesitancy in different demographic groups.

Community perceptions and experiences on the events leading to facility maternal death; a verbal autopsy qualitative study.

BACKGROUND: Tanzania Maternal Death Surveillance and Response (MDSR) system introduced in 2015 emphasizes review of facility maternal deaths with little community involvement. Involving the community in deaths enquiry can help to make better strategies to prevent future deaths. We aimed to explore family members (caregivers) perceptions and experiences on the events leading to facility maternal deaths to inform future community involvement in MDSR. METHODS: Narrative interviews were conducted with 20 caregivers who cared for women who died in childbirth to investigate into delays and health care seeking experience. The unstructured questions on perceptions and experiences of events leading to death were administered together with standard verbal autopsy questionnaire. Two regions, Lindi and Mtwara of Southern Tanzania were selected for the study in 2018. Narrative thematic analysis was used for data analysis. RESULTS: Three main themes evolved: 'Prepared for birth but not ready for complications', 'Disconnect between caregivers and providers' and 'The bitter impact of maternal deaths. Caregivers made efforts to prepare for birth but their preparation were severely inadequate when complications that necessitated referral occurred. Decision to seek care was made jointly between the pregnant woman, husband and other family members. Caregivers tried with little success in communicating with heathcare providers regarding their admitted patients. They also experienced emotions of grief such as denial, anger, depression, bargaining and acceptance once maternal deaths occurred. Caregivers (mostly old women) were left with the burden of caring for the newborns and other children left by the deceased mother. CONCLUSION: Caregivers' perceptions and experiences of maternal deaths events provide valuable information for community interventions on birth preparedness, decision making, communication and providers' accountability. Maternal deaths bring far reaching mental, social and economic consequences to the family and society.

Regional Evaluation of Two SARS-CoV-2 Antigen Rapid Diagnostic Tests in East Africa.

The clinical performance of two rapid antigen tests for the diagnosis of Severe Acute Respiratory Coronavirus (SARS-CoV-2) were regionally evaluated in East African populations. Swabs were collected from 1,432 individuals from five Partner States of the East African Community (Tanzania, Uganda, Burundi, Rwanda and South Sudan). The two rapid antigen tests (Bionote NowCheck COVID-19 Ag and SD Biosensor STANDARD Q COVID-19 Ag) were evaluated against the detection of SARS-CoV-2 RNA by the Reverse Transcription PCR (RT-PCR) gold standard. Of the concordant results with both RT-PCR and rapid antigen test data (862 for Bionote and 852 for SD Biosensor), overall clinical sensitivity was 60% and 50% for the Bionote NowCheck and the SD Biosensor STANDARD Q, respectively. Stratification by viral load, including samples with RT-PCR cycle thresholds (Ct) of <25, improved sensitivity to 90% for both rapid diagnostic tests (RDTs). Overall specificity was good at 99% for both antigen tests. Taken together, the clinical performance of both Ag-RDTs in real world settings within the East African target population was lower than has been reported elsewhere and below the acceptable levels for sensitivity of >80%, as defined by the WHO. Therefore, the rapid antigen test alone should not be used for diagnosis but could be used as part of an algorithm to identify potentially infectious individuals with high viral load. IMPORTANCE Accurate diagnostic tests are essential to both support the management and containment of outbreaks, as well as inform appropriate patient care. In the case of the SARS-CoV-2 pandemic, antigen Rapid Diagnostic Tests (Ag-RDTs) played a major role in this function, enabling widespread testing by untrained individuals, both at home and within health facilities. In East Africa, a number of SARS-CoV-2 Ag-RDTs are available; however, there remains little information on their true test performance within the region, in the hands of the health workers routinely carrying out SARS-CoV-2 diagnostics. This study contributes test performance data for two commonly used SARS-CoV-2 Ag-RDTs in East Africa, which will help inform the use of these RDTs within the region.

RIPK1 inhibition contributes to lysosomal membrane stabilization in ischemic astrocytes via a lysosomal Hsp70.1B-dependent mechanism.

Receptor-interacting protein kinase 1 (RIPK1) contributes to necroptosis. Our previous study showed that pharmacological or genetic inhibition of RIPK1 protects against ischemic stroke-induced astrocyte injury. In this study, we investigated the molecular mechanisms underlying RIPK1-mediated astrocyte injury in vitro and in vivo. Primary cultured astrocytes were transfected with lentiviruses and then subjected to oxygen and glucose deprivation (OGD). In a rat model of permanent middle cerebral artery occlusion (pMCAO), lentiviruses carrying shRNA targeting RIPK1 or shRNA targeting heat shock protein 70.1B (Hsp70.1B) were injected into the lateral ventricles 5 days before pMCAO was established. We showed that RIPK1 knockdown protected against OGD-induced astrocyte damage, blocked the OGD-mediated increase in lysosomal membrane permeability in astrocytes, and inhibited the pMCAO-induced increase in astrocyte lysosome numbers in the ischemic cerebral cortex; these results suggested that RIPK1 contributed to the lysosomal injury in ischemic astrocytes. We revealed that RIPK1 knockdown upregulated the protein levels of Hsp70.1B and increased the colocalization of Lamp1 and Hsp70.1B in ischemic astrocytes. Hsp70.1B knockdown exacerbated pMCAO-induced brain injury, decreased lysosomal membrane integrity and blocked the protective effects of the RIPK1-specific inhibitor necrostatin-1 on lysosomal membranes. On the other hand, RIPK1 knockdown further exacerbated the pMCAO- or OGD-induced decreases in the levels of Hsp90 and the binding of Hsp90 to heat shock transcription factor-1 (Hsf1) in the cytoplasm, and RIPK1 knockdown promoted the nuclear translocation of Hsf1 in ischemic astrocytes, resulting in increased Hsp70.1B mRNA expression. These results suggest that inhibition of RIPK1 protects ischemic astrocytes by stabilizing lysosomal membranes via the upregulation of lysosomal Hsp70.1B; the mechanism underlying these effects involves decreased Hsp90 protein levels, increased Hsf1 nuclear translocation and increased Hsp70.1B mRNA expression.

Data from the batch adsorption of ciprofloxacin and lamivudine from synthetic solution using jamun seed (Syzygium cumini) biochar: Response surface methodology (RSM) optimization.

This dataset expresses the experimental data on the batch adsorption of ciprofloxacin and lamivudine from synthetic solution using jamun seed (JS) (Syzygium cumini) biochar. Independent variables including concentration of pollutants (10-500 ppm), contact time (30-300 min), adsorbent dosage (1-1000 mg), pH (1-14) and adsorbent calcination temperature (250,300, 600 and 750 °C) were studied and optimized using Response Surface Methodology (RSM). Empirical models were developed to predict the maximum removal efficiency of ciprofloxacin and lamivudine, and the results were compared with the experimental data. The removal of polutants was more influenced by concentration, followed by adsorbent dosagage, pH, and contact time and the maximum removal reached 90%.

Therapeutic potential of vitamin D against bisphenol A-induced spleen injury in Swiss albino mice.

Bisphenol A (BPA), a ubiquitous plasticizer, is capable of producing oxidative splenic injury, and ultimately led to spleen pathology. Further, a link between VitD levels and oxidative stress was reported. Hence the role of VitD in BPA-induced oxidative splenic injury was investigated in this study. Sixty male and female Swiss albino mice (3.5 weeks old) were randomly divided into control and treated groups 12 mice in each (six males and six females). The control groups were further divided into sham (no treatment) and vehicle (sterile corn oil), whereas the treatment group was divided into VitD (2,195 IU/kg), BPA (50 µg/kg), and BPA+VitD (50 µg/kg + 2,195 IU/kg) groups. For six weeks, the animals were dosed intraperitoneally (i.p). One week later, at 10.5 weeks old, mice were sacrificed for biochemical and histological analyses. Findings showed BPA triggered neurobehavioral abnormalities and spleen injury with increased apoptotic indices (e.g. DNA fragmentation) in both sexes. A significant increase was found in lipid peroxidation marker, MDA in splenic tissue, and leukocytosis. Conversely, VitD treatment altered this scenario into motor performance preservation, reducing oxidative splenic injury with a decrease in the percent apoptotic index. This protection was significantly correlated with preserving leukocyte counts and reduced MDA levels in both genders. It can be concluded from the above findings that VitD treatment has an ameliorative effect on oxidative splenic injury induced by BPA, highlighting the continuous crosstalk between oxidative stress and the VitD signaling pathway.

A comparative in-vitro study on antimicrobial efficacy of on-market alcohol-based hand washing sanitizers towards combating microbes and its application in combating Covid-19 global outbreak.

The coronavirus disease 2019 (COVID-19) outbreak has created endless social, economic, and political fear in the global human population. Measures employed include frequent washing hands and using alcohol-based hand sanitisers and hand rubs as instant hand hygiene products. Due to the need to mitigate the pandermic, there is an increase in the local production of alcohol-based hand sanitisers, whose quality and efficacy against germs and the virus are questionable. Therefore, the current study investigated the in-vitro antimicrobial efficacy of on-market alcohol-based handwashing sanitizers used to mitigate the Covid-19 global outbreak toward combating enveloped bacteria such as E. Coli, P. aeroginosa, S. aureus, and a fungus C. albicans. The antimicrobial effectiveness of alcohol-based hand sanitizer was performed by the agar well diffusion method, and the analysis of variance (ANOVA) model was used for statistical analysis. Results indicate that alcohol hand-based sanitizers were more effective in inhibiting P. aeroginosa, with a mean zone of inhibition of 12.47 mm, followed by E. coli, a gram-negative bacterium with a mean zone of inhibition of 12.13 mm than both S. aureus and C. albicans as gram-positive bacteria, and fungi respectively had the same inhibition average of 11.40 mm. The overall mean diameter of inhibition was statistically significantly different among the fifteen tested products. Only one brand of alcohol-based hand sanitizers was the most effective in inhibiting microbes. Less effective sanitizers may impair Covid 19 mitigation efforts and put the population at risk instead of protecting it. Indicating the need for all materials used to mitigate Covid 19 pandermic, including alcohol-based hand sanitizers, to be evaluated and monitored to ensure public health safety.

Geochemical, Mineralogical, and Geomorphological Characterization of Ash Materials as a Tracer for the Origin of Shifting Sands near Oldupai Gorge, Ngorongoro, Tanzania.

Shifting sand (SS) is a single dune-shaped mass of black ash material moving across western Ngorongoro in northern Tanzania. The moving sand has become an important tourist destination for several decades. Despite being part of the important geosites at the Ngorongoro Conservation Area, the nature, origin, and behaviors demonstrated by SS remain poorly understood. This work contributes toward understanding the nature and identification of the possible origin of the SS through the correlation of geochemical, mineralogical, and geomorphological data of ash material from four selected locations in the study area. To achieve this goal, elemental, mineralogical, and morphological characterization of ash samples was performed by energy-dispersive X-ray fluorescence, polarized petrographic microscopy, automated sieve shaker, and binocular microscopy techniques, respectively. Correlation studies were based on magnesian-ferriferous associations, similarities in mineralogy, particle size, shape, and distribution patterns of ash materials, and weather data. There are close similarities in the chemical compositions among ash samples of SS, Ootun area, and Oldoinyo Lengai. Augite and magnetite minerals appear only in samples of SS, Ootun area, and Oldoinyo Lengai, while hornblende appears only in the samples from the Ngorongoro crater. Oldoinyo Lengai rock petrography revealed significant amounts of augite minerals. Blocky and elongated-shaped ash particles dominate the samples from SS, Ootun area, and Oldoinyo Lengai. The particle size of ash materials decreases westwards across the study site. The distribution patterns of ash material align with the west-south-west wind direction. Based on these findings, the study concludes that SS and Ootun ash could be tephra depositions resulting from past volcanic eruptions of Oldoinyo Lengai.

Continued disruptions in health care services and mental health among health care providers during the COVID-19 pandemic in five sub-Saharan African countries.

Background: Continuous monitoring of the pandemic's impact on health service provision and mental health, COVID-19 perceptions, and compliance with prevention measures among health care providers (HCPs) can help with mitigating the pandemic's negative effects. Methods: A computer-assisted telephone interviewing (CATI) survey was conducted among 1499 HCPs in Burkina Faso (Ouagadougou), Ethiopia (Addis Ababa), Nigeria (Lagos and Ibadan), Tanzania (Dar es Salaam), and Ghana (Kintampo). Self-reported mental health, perceptions of the COVID-19 pandemic, and prevention measures available in the workplace were assessed. HCPs' responses to questions regarding the impact of COVID-19 on nine essential health services were summed into a score; high service disruption was defined as a score higher than the total average score across all sites. Modified Poisson regression was used to identify potential factors related to high service disruption. Results: Overall, 26.9% of HCPs reported high service disruption, with considerable differences across sites (from 1.6% in Dar es Salaam to 45.0% in Addis Ababa). A considerable proportion of HCPs reported experiencing mild psychological distress (9.4%), anxiety (8.0%), and social avoidance or rejection (13.9%) due to their profession. Participants in Addis Ababa (absolute risk ratio (ARR) = 2.10; 95% confidence interval (CI) = 1.59-2.74), Lagos (ARR = 1.65; 95% CI = 1.24-2.17), and Kintampo (ARR = 2.61; 95% CI = 1.94-3.52) had a higher likelihood of reporting high service disruption compared to those in Ouagadougou. Reporting ever-testing for COVID-19 (ARR = 0.82; 95% CI = 0.69-0.97) and the presence of COVID-19 guidelines in the workplace (ARR = 0.63; 95% CI = 0.53-0.77) were both associated with lower reported health service disruption among HCPs. Conclusion: The COVID-19 pandemic continues to disrupt essential health services and present a challenge to HCPs' mental health, with important differences across countries and settings; interventions are needed to mitigate these negative effects of the pandemic.

Attenuation of nitrate from aqueous solution using raw and surface modified biosorbents from Adansonia digitata fruit pericarp.

The prevalence of nitrate in potable water is a serious environmental concern. Several methods for eliminating nitrate from water have been made and implemented. During the course of this research, raw (RADFP) and surface-modified fruit pericarp (SMADFP) biosorbents derived from the Adansonia digitata plant were applied in order to remove nitrate from an aqueous solution. The external features of the biosorbents were studied with the aids of SEM and BET. The FT-IR spectrometer was utilized for identification of the functional groups of the adsorbents. A UV-Vis device was used to quantify the nitrate concentration. The adsorbents under investigation exhibit a heterogeneous pore structure with a considerable number of mesopores, with surface areas of 361.527 and 379.877 m2 per gram for RADFP and SMADFP, respectively. FT-IR spectra revealed the presence of carboxyl, hydroxyl, carbonyl, and halogen groups on the adsorbent. The maximum nitrate removal efficiencies of RADFP and SMADFP were 64.55 and 88.95%, respectively. The maximum adsorption efficiencies are achieved when the pH is 2, the starting concentration is 27.50 mg/L, the contact period is 75.00 min, and the amount of biosorbent is 5.50 g. RADFP and SMADFP have a removal capacity of 12.45 as well as 25.18 mg per gram and adsorption intensity of 3.2300 and 5.4500, respectively. The investigational values for the elimination of nitrate ions concurred well to both Freundlich and Langmuir models with R2 values of 0.99917 and 0.99763 for RADFP and SMADFP, respectively, and pseudo-second-order kinetic model with R2 values of 0.99817 and 0.99947, respectively for RADFP and SMADFP. It can be concluded that SMADFP is a relatively better biosorbent than RADFP, which will be utilizable for the remediation of nitrate from an aqueous solution.

High-glucose-induced hyperosmolar stress sensitizes HepG2 cell lines to sorafenib.

Sorafenib is an FDA approved chemotherapeutic against hepatocellular carcinoma (HCC) yet associated with various resistance mechanisms. The role of high glucose status on sorafenib action is still to be elucidated. This study clarifies such interaction, taking HepG2 cell lines as HCC models, MALAT1 and H19 as molecular players. HepG2 cell lines were purchased and classified into 8 groups. High glucose status was set by using d-glucose (33 mM) with insulin (1 µM). Mannitol (27.5 mM) was used as a negative osmotic control. Sorafenib was prepared at 15 µM and 20 µM. Cellular viability was assessed with MTT viability assay. Then, with trypan blue viability assay, the results were double checked and HepG2 morphology was examined by optical microscopy. MALAT1 and H19 RQs were assessed by real time PCR (RT-PCR). Results show that in comparison with sorafenib impact on HepG2, high glucose status drops cellular viability to 83.13 % (p < 0.01). With hyperosmolar mannitol, it decreases cellular viability to 72.89 % (p < 0.001). Regarding the molecular impact, hyperosmolar mannitol with sorafenib elevates both MALAT1 and H19 RQs. Yet, high glucose status elevates MALAT1and declines H19 (p < 0.05 and p < 0.001 for MALAT1 and H19 comparisons respectively). Therefore, the impact of high glucose status could be, in part, attributed to the hyperosmolar stress it induces on HepG2. Also, hyperosmolar mannitol, owing to its cytotoxic impact, is recommended for further confirmatory studies either as a separate therapeutic or as an adjuvant to sorafenib.

Comparative efficacy of lidocaine-prilocaine cream and vaginal misoprostol in reducing pain during levonorgestrel intrauterine device insertion in women delivered only by cesarean delivery: A randomized controlled trial.

OBJECTIVE: To compare efficacy of lidocaine-prilocaine (LP) cream versus misoprostol versus placebo before levonorgestrel-releasing intrauterine device (LNG-IUD) insertion. METHODS: This randomized controlled trial (RCT) was conducted in a tertiary referral hospital from April 30, 2020 to March 1, 2021 on 210 parous women willing to receive LNG-IUD and delivered only by elective cesarean delivery (CD). Participants received 200 µg vaginal misoprostol or 5 ml of LP cream 5% or placebo 3 h before LNG-IUS insertion. Primary outcome was pain during LNG-IUD insertion, while secondary outcomes were pain 10 min post-procedure, ease of insertion, patient satisfaction, insertion time, and drug side effects. RESULTS: Pain during LNG-IUS insertion was reduced in LP group and misoprostol group compared to placebo group (2.1 ± 1.0 vs 3.7 ± 1.6; p <0.001) and (2.3 ± 1.3 vs 3.7 ± 1.6; p <0.001), respectively. Ease of procedure and patient satisfaction were significantly higher in LP and misoprostol groups than placebo (P <0.001). Need for additional analgesia was significantly higher in placebo group than in the other two groups (P = 0.009). Adverse events were not significantly different between the three groups except vomiting and abdominal cramps, which were higher with misoprostol. CONCLUSION: LP cream and 200 µg of vaginal misoprostol administration before LNG-IUD insertion in women delivered only by elective CD effectively reduced pain during insertion and 10 min post-procedure with easier insertions, high patient satisfaction, and tolerable side effects. Pain reduction with LP cream was clinically significant.

A comparative study of estimators in multilevel linear models.

Multilevel Models are widely used in organizational research, educational research, epidemiology, psychology, biology and medical fields. In this paper, we recommend the situations where Bootstrap procedures through Minimum Norm Quadratic Unbiased Estimator (MINQUE) can be extremely handy than that of Restricted Maximum Likelihood (REML) in multilevel level linear regression models. In our simulation study the bootstrap by means of MINQUE is superior to REML in conditions where normality does not hold. Moreover, the real data application also supports our findings in terms of accuracy of estimates and their standard errors.

Intussusception among infants in Tanzania: findings from prospective hospital-based surveillance, 2013-2016.

INTRODUCTION: intussusception surveillance was initiated in Tanzania in 2013 after monovalent rotavirus vaccine was introduced, as part of the 7-country African evaluation to assess whether the vaccine was associated with an increased risk of intussusception. An increased risk from vaccine was not identified. Published data on intussusception in Tanzanian infants are limited. METHODS: prospective intussusception surveillance was conducted at 7 referral hospitals during 2013-2016 to identify all infants with intussusception meeting Brighton Level 1 criteria. Demographic, household and clinical data were collected by hospital clinicians and analyzed. RESULTS: a total of 207 intussusception cases were identified. The median age of cases was 5.8 months and nearly three-quarters were aged 4-7 months. Median number of days from symptom onset to admission at treatment hospital was 3 (IQR 2-5). Seventy-eight percent (152/195) of cases had been admitted at another hospital before transfer to the treating hospital. Enema reduction was not available; all infants were treated surgically and 55% (114/207) had intestinal resection. The overall case-fatality rate was 30% (62/206). Compared with infants who survived, those who died had longer duration of symptoms before admission to treatment hospital (median 4 vs 3 days; p < 0.01), higher rate of intestinal resection (81% [60/82] vs 44% [64/144], p < 0.001), and from families with lower incomes (i.e., less likely to own a television [p < 0.01] and refrigerator [p < 0.05). CONCLUSION: Tanzanian infants who develop intussusception have a high case-fatality rate. Raising the index of suspicion among healthcare providers, allocating resources to allow wider availability of abdominal ultrasound for earlier diagnosis, and training teams in ultrasound-guided enema reduction techniques used in other African countries could reduce the fatality rate.

Incidence of Plasmodium falciparum malaria infection in 6-month to 45-year-olds on selected areas of Bioko Island, Equatorial Guinea.

BACKGROUND: Extensive malaria control measures have been implemented on Bioko Island, Equatorial Guinea over the past 16 years, reducing parasite prevalence and malaria-related morbidity and mortality, but without achieving elimination. Malaria vaccines offer hope for reducing the burden to zero. Three phase 1/2 studies have been conducted successfully on Bioko Island to evaluate the safety and efficacy of whole Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccines. A large, pivotal trial of the safety and efficacy of the radiation-attenuated Sanaria® PfSPZ Vaccine against P. falciparum is planned for 2022. This study assessed the incidence of malaria at the phase 3 study site and characterized the influence of socio-demographic factors on the burden of malaria to guide trial design. METHODS: A cohort of 240 randomly selected individuals aged 6 months to 45 years from selected areas of North Bioko Province, Bioko Island, was followed for 24 weeks after clearance of parasitaemia. Assessment of clinical presentation consistent with malaria and thick blood smears were performed every 2 weeks. Incidence of first and multiple malaria infections per person-time of follow-up was estimated, compared between age groups, and examined for associated socio-demographic risk factors. RESULTS: There were 58 malaria infection episodes observed during the follow up period, including 47 first and 11 repeat infections. The incidence of malaria was 0.25 [95% CI (0.19, 0.32)] and of first malaria was 0.23 [95% CI (0.17, 0.30)] per person per 24 weeks (0.22 in 6-59-month-olds, 0.26 in 5-17-year-olds, 0.20 in 18-45-year-olds). Incidence of first malaria with symptoms was 0.13 [95% CI (0.09, 0.19)] per person per 24 weeks (0.16 in 6-59-month-olds, 0.10 in 5-17-year-olds, 0.11 in 18-45-year-olds). Multivariate assessment showed that study area, gender, malaria positivity at screening, and household socioeconomic status independently predicted the observed incidence of malaria. CONCLUSION: Despite intensive malaria control efforts on Bioko Island, local transmission remains and is spread evenly throughout age groups. These incidence rates indicate moderate malaria transmission which may be sufficient to support future larger trials of PfSPZ Vaccine. The long-term goal is to conduct mass vaccination programmes to halt transmission and eliminate P. falciparum malaria.

Mismatched ambition, execution and outcomes: implementing maternal death surveillance and response system in Mtwara region, Tanzania.

BACKGROUND: Since 2015, Tanzania has been implementing the Maternal Death Surveillance and Response (MDSR) system. The system employs interactions of health providers and managers to identify, notify and review maternal deaths and recommend strategies for preventing further deaths. We aimed to analyse perceptions and experiences of health providers and managers in implementing the MDSR system. METHODS: An exploratory qualitative study was carried out with 30 purposively selected health providers and 30 health managers in four councils from the Mtwara region between June and July 2020. Key informant interviews and focus group discussions were used to collect data. Inductive thematic analysis was used to analyse data. RESULTS: Two main themes emerged from this study: 'Accomplishing by ambitions' and 'A flawed system'. The themes suggest that health providers and managers have a strong desire to make the MDSR system work by making deliberate efforts to implement it. They reported working hard to timely notify, review death and implement action plans from meetings. Health providers and managers reported that MDSR has produced changes in care provision such as behavioural changes towards maternal care, increased accountability and policy changes. The system was however flawed by lack of training, organisational problems, poor coordination with other reporting and quality improvements systems, assigning blame and lack of motivation. CONCLUSION: The implementation of the MDSR system in Tanzania faces systemic, contextual and individual challenges. However, our results indicate that health providers and managers are willing and committed to improve service delivery to avoid maternal deaths. Empowering health providers and managers by training and addressing the flaws will improve the system and quality of care.

Maternal death surveillance and response in Tanzania: comprehensiveness of narrative summaries and action points from maternal death reviews.

BACKGROUND: Maternal deaths reviews are proposed as one strategy to address high maternal mortality in low and middle-income countries, including Tanzania. Review of maternal deaths relies on comprehensive documentation of medical records that can reveal the sequence of events leading to death. The World Health Organization's and the Tanzanian Maternal Death and Surveillance (MDSR) system propose the use of narrative summaries during maternal death reviews for discussing the case to categorize causes of death, identify gaps in care and recommend action plans to prevent deaths. Suggested action plans are recommended to be Specific, Measurable, Attainable, Relevant and Time bound (SMART). To identify gaps in documenting information and developing recommendations, comprehensiveness of written narrative summaries and action plans were assessed. METHODS: A total of 76 facility maternal deaths that occurred in two regions in Southern Tanzania in 2018 were included for analysis. Using a prepared checklist from Tanzania 2015 MDSR guideline, we assessed comprehensiveness by presence or absence of items in four domains, each with several attributes. These were socio-demographic characteristics, antenatal care, referral information and events that occurred after admission. Less than 75% completeness of attributes in all domains was considered poor while 95% and above were good/comprehensive. Action plans were assessed by application of SMART criteria and according to the place of planned implementation (community, facility or higher level of health system). RESULTS: Almost half of narrative summaries (49%) scored poor, and only1% scored good/comprehensive. Summaries missed key information such as demographic characteristics, time between diagnosis of complication and commencing treatment (65%), investigation results (47%), summary of case evolution (51%) and referral information (47%). A total of 285 action points were analysed. Most action points, 242(85%), recommended strategies to be implemented at health facilities and were mostly about service delivery, 120(42%). Only 42% (32/76) of the action points were deemed to be SMART. CONCLUSIONS: Abstraction of information to prepare narrative summaries used in the MDSR system is inadequately done. Most recommendations were unspecific with a focus on improving quality of care in health facilities.