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Antimicrobial resistance is a global health threat and efforts to mitigate it is warranted, thus the need for local antibiograms to improve stewardship. This study highlights the process that was used to develop an antibiogram to monitor resistance at a secondary-level health facility to aid empirical clinical decision making in a sub-Saharan African county. This retrospective cross-sectional descriptive study used 3 years of cumulative data from January 2016 to December 2018. Phenotypic data was manually imputed into WHONET and the cumulative antibiogram constructed using standardized methodologies according to CLSI M39-A4 guidelines. Pathogens were identified by standard manual microbiological methods and antimicrobial susceptibility testing was performed using Kirby-Bauer disc diffusion method according to CLSI M100 guidelines. A total of 14,776 non-duplicate samples were processed of which 1163 (7.9%) were positive for clinically significant pathogens. Among the 1163 pathogens, E. coli (n = 315) S. aureus (n = 232), and K. pneumoniae (n = 96) were the leading cause of disease. Overall, the susceptibility for E. coli and K. pneumoniae from all samples were: trimethoprim-sulfamethoxazole (17% and 28%), tetracycline (26% and 33%), gentamicin (72% and 46%), chloramphenicol (76 and 60%), and ciprofloxacin (69% and 59%), and amoxicillin/clavulanic (77% and 54%) respectively. Extended spectrum beta-lactamase (ESBL) resistance was present in 23% (71/315) vs. 35% (34/96) respectively. S. aureus susceptibility for methicillin was 99%. This antibiogram has shown that improvement in combination therapy is warranted in The Gambia.

By the end of October 2020, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic had spread to 6 continents and caused >45 million coronavirus disease (COVID-19) cases and 1.1 [...]

Exposure to extreme heat in pregnancy increases the risk of stillbirth. Progress in reducing stillbirth rates has stalled, and populations are increasingly exposed to high temperatures and climate events that may further undermine health strategies. This narrative review summarises the current clinical and epidemiological evidence of the impact of maternal heat exposure on stillbirth risk. Out of 20 studies, 19 found an association between heat and stillbirth risk. Recent studies based in low‐ to middle‐income countries and tropical settings add to the existing literature to demonstrate that all populations are at risk. Additionally, both short‐term heat exposure and whole‐pregnancy heat exposure increase the risk of stillbirth. A definitive threshold of effect has not been identified, as most studies define exposure as above the 90th centile of the usual temperature for that population. Therefore, the association between heat and stillbirth has been found with exposures from as low as >12.64°C up to >46.4°C. The pathophysiological pathways by which maternal heat exposure may lead to stillbirth, based on human and animal studies, include both placental and embryonic or fetal impacts. Although evidence gaps remain and further research is needed to characterise these mechanistic pathways in more detail, preliminary evidence suggests epigenetic changes, alteration in imprinted genes, congenital abnormalities, reduction in placental blood flow, size and function all play a part. Finally, we explore this topic from a public health perspective; we discuss and evaluate the current public health guidance on minimising the risk of extreme heat in the community. There is limited pregnancy‐specific guidance within heatwave planning, and no evidence‐based interventions have been established to prevent poor pregnancy outcomes. We highlight priority research questions to move forward in the field and specifically note the urgent need for evidence‐based interventions that are sustainable. [ABSTRACT FROM AUTHOR]

Background Current artesunate (ARS) regimens for severe malaria are complex. Once daily intramuscular (i.m.) injection for 3 d would be simpler and more appropriate for remote health facilities than the current WHO-recommended regimen of five intravenous (i.v.) or i.m. injections over 4 d. We compared both a three-dose i.m. and a three-dose i.v. parenteral ARS regimen with the standard five-dose regimen using a non-inferiority design (with non-inferiority margins of 10%). Methods and Findings This randomized controlled trial included children (0.5-10 y) with severe malaria at seven sites in five African countries to assess whether the efficacy of simplified three-dose regimens is non-inferior to a five-dose regimen. We randomly allocated 1,047 children to receive a total dose of 12 mg/kg ARS as either a control regimen of five i.m. injections of 2.4 mg/kg (at 0,12, 24, 48, and 72 h) (n = 348) or three injections of 4 mg/kg (at 0,24, and 48 h) either i.m. (n = 348) or i.v. (n = 351), both of which were the intervention arms. The primary endpoint was the proportion of children with >99% reduction in parasitemia at 24 h from admission values, measured by microscopists who were blinded to the group allocations. Primary analysis was performed on the per-protocol population, which was 96% of the intention-to-treat population. Secondary analyses included an analysis of host and parasite genotypes as risks for prolongation of parasite clearance kinetics, measured every 6 h, and a Kaplan-Meier analysis to compare parasite clearance kinetics between treatment groups. A post hoc analysis was performed for delayed anemia, defined as hemoglobin ≤ 7g/dl 7 d or more after admission. The per-protocol population was 1,002 children (five-dose i.m.: n = 331; three-dose i.m.: n = 338; three-dose i.v.: n = 333); 139 participants were lost to follow-up. In the three-dose i. m. arm, 265/338 (78%) children had a >99% reduction in parasitemia at 24 h compared to 263/331 (79%) receiving the five-dose i.m. regimen, showing non-inferiority of the simplified three-dose regimen to the conventional five-dose regimen (95% CI -7,5; p = 0.02). In the three-dose i.v. arm, 246/333 (74%) children had ≥ 99% reduction in parasitemia at 24 h; hence, non-inferiority of this regimen to the five-dose control regimen was not shown (95% CI -12,1; p = 0.24). Delayed parasite clearance was associated with the [sup.N86Y]Pfmdr1 genotype. In a post hoc analysis, 192/885 (22%) children developed delayed anemia, an adverse event associated with increased leukocyte counts. There was no observed difference in delayed anemia between treatment arms. A potential limitation of the study is its open-label design, although the primary outcome measures were assessed in a blinded manner. Conclusions A simplified three-dose i.m. regimen for severe malaria in African children is non-inferior to the more complex WHO-recommended regimen. Parenteral ARS is associated with a risk of delayed anemia in African children. Trial registration Pan African Clinical Trials Registry PACTR201102000277177, Introduction Studies to optimize artesunate (ARS) treatment regimens in malaria have been surprisingly sparse, given that ARS is now established as the treatment of choice for severe malaria in both [...]

Abstract Background HIV infection among children, particularly those under 24 months of age, is often rapidly progressive; as a result guidelines recommend earlier access to combination antiretroviral therapy (cART) for HIV infected children. Losses to follow-up (LTFU) and death in the interval between diagnosis and initiation of ART profoundly limit this strategy. This study explores correlates of LTFU and death prior to ART initiation among children. Methods The study is based on 337 HIV-infected children enrolled into care at an urban centre in The Gambia, including those alive and in care when antiretroviral therapy became available and those who enrolled later. Children were followed until they started ART, died, transferred to another facility, or were LTFU. Cox proportional hazards regression models were used to determine the hazard of death or LTFU according to the baseline characteristics of the children. Results Overall, 223 children were assessed as eligible for ART based on their clinical and/or immunological status among whom 73 (32.7%) started treatment, 15 (6.7%) requested transfer to another health facility, 105 (47.1%) and 30 (13.5%) were lost to follow-up and died respectively without starting ART. The median survival following eligibility for children who died without starting treatment was 2.8 months (IQR: 0.9 - 5.8) with over half (60%) of all deaths occurring at home. ART-eligible children less than 2 years of age and those in WHO stage 3 or 4 were significantly more likely to be LTFU when compared with their respective comparison groups. The overall pre-treatment mortality rate was 25.7 per 100 child-years of follow-up (95% CI 19.9 - 36.8) and the loss to programme rate was 115.7 per 100 child-years of follow-up (95% CI 98.8 - 137). In the multivariable Cox proportional hazard model, significant independent predictors of loss to programme were being less than 2 years of age and WHO stage 3 or 4. The Adjusted Hazard Ratio (AHR) for loss to programme was 2.06 (95% CI 1.12 – 3.83) for being aged less than 2 years relative to being 5 years of age or older and 1.92 (95% CI 1.05 - 3.53) for being in WHO stage 3 or 4 relative to WHO stage 1 or 2. Conclusions Earlier enrolment into HIV care is key to achieving better outcomes for HIV infected children in developing countries. Developing strategies to ensure early diagnosis, elimination of obstacles to prompt initiation of therapy and instituting measures to reduce losses to follow-up, will improve the overall outcomes of HIV-infected children.

Abstract Background There is little data on responses to combination antiretroviral therapy (cART) among HIV-infected children in the West African region. We describe treatment outcomes among HIV-1 and HIV-2 infected children initiating cART in a research clinic in The Gambia, West Africa. Methods All treatment naive HIV-infected children who initiated cART according to the WHO ART guidelines for children between October 2004 and December 2009 were included in the analysis. Kaplan-Meir estimates and sign-rank test were used to investigate the responses to treatment. Results 65 HIV-1 and five HIV-2 infected children aged 10 copies/ml (4.4 – 6.0) respectively. The median age at treatment initiation of the five HIV-2 infected children was 12 years (range: 4.6 – 14.0) while their median baseline CD4+ T cell count and HIV-2 viral load were 140 cells/mm3 (Range: 40 – 570 cells/mm3) and 4.5 log10copies/mL (Range: 3.1 - 4.9 log10copies/mL) respectively. Among HIV-1 infected children P = 0.0004), 21% (15 – 22; P = 0.005) and 15% (15 – 25; P = 0.0422) respectively, while the median (IQR) increase in absolute CD4 T cell count from baseline to 12, 24 and 36 months for those ≥5 years at ART initiation were 470 cells/mm3 (270 – 650; P = 0.0005), 230 cells/mm3 (30 – 610; P = 0.0196) and 615 cells/mm3 (250 – 1060; P = 0.0180) respectively. The proportions of children achieving undetectable HIV-1 viral load at 6-, 12-, 24- and 36 months of treatment were 24/38 (63.2%), 20/36 (55.6%), 8/22 (36.4%) and 7/12 (58.3%) respectively. The probability of survival among HIV-1 infected children after 12 months on ART was 89.9% (95% CI 78.8 – 95.3). CD4 T cell recovery was sub-optimal in all the HIV-2 infected children and none achieved virologic suppression. Two of the HIV-2 infected children died within 6 months of starting treatment while the remaining three were lost to follow-up. Conclusions The beneficial effects of cART among HIV-1 infected children in our setting are sustained in the first 24 months of treatment with a significant improvement in survival experience up to 36 months; however the outcome was poor in the few HIV-2 infected children initiated on cART.

Abstract Background High early mortality rate among HIV infected patients following initiation of antiretroviral therapy (ART) in resource limited settings may indicate high pre-treatment mortality among ART-eligible patients. There is dearth of data on pre-treatment mortality in ART programmes in sub-Sahara Africa. This study aims to determine pre-treatment mortality rate and predictors of pre-treatment mortality among ART-eligible adult patients in a West Africa clinic-based cohort. Methods All HIV-infected patients aged 15 years or older eligible for ART between June 2004 and September 2009 were included in the analysis. Assessment for eligibility was based on the Gambia ART guideline. Survival following ART-eligibility was determined by Kaplan-Meier estimates and predictors of pre-treatment mortality determined by Cox proportional hazard models. Result Overall, 790 patients were assessed as eligible for ART based on their clinical and/or immunological status among whom 510 (64.6%) started treatment, 26 (3.3%) requested transfer to another health facility, 136 (17.2%) and 118 (14.9%) were lost to follow-up and died respectively without starting ART. ART-eligible patients who died or were lost to follow-up were more likely to be male or to have a CD4 T-cell count < 100 cells/μL, while patients in WHO clinical stage 3 or 4 were more likely to die without starting treatment. The overall pre-treatment mortality rate was 21.9 deaths per 100 person-years (95% CI 18.3 - 26.2) and the rate for the composite end point of death or loss to follow-up was 47.1 per 100 person-years (95% CI 41.6 - 53.2). Independent predictors of pre-treatment mortality were CD4 T-cell count Conclusion Approximately one third of ART-eligible patients did not start ART and pre-treatment mortality rate was found high among HIV infected patients in our cohort. CD4 T-cell count

Abstract Background Nigeria's national standard has recently moved to artemisinin combination treatments for malaria. As clinicians in the private sector are responsible for attending a large proportion of the population ill with malaria, this study compared prescribing in the private and public sector in one State in Nigeria prior to promoting ACTs. Objective To assess prescribing for uncomplicated malaria in government and private health facilities in Cross River State. Method Audit of 665 patient records at six private and seven government health facilities in 2003. Results Clinicians in the private sector were less likely to record history or physical examination than those in public facilities, but otherwise practice and prescribing were similar. Overall, 45% of patients had a diagnostic blood slides; 77% were prescribed monotherapy, either chloroquine (30.2%), sulphadoxine-pyrimethamine (22.7%) or artemisinin derivatives alone (15.8%). Some 20.8% were prescribed combination therapy; the commonest was chloroquine with sulphadoxine-pyrimethamine. A few patients (3.5%) were prescribed sulphadoxine-pyrimethamine-mefloquine in the private sector, and only 3.0% patients were prescribed artemisinin combination treatments. Conclusion Malaria treatments were varied, but there were not large differences between the public and private sector. Very few are following current WHO guidelines. Monotherapy with artemisinin derivatives is relatively common.