Spatio-temporal pattern of short birth interval and associated factors on women in Ethiopia: Using Ethiopian demographic and health surveys 2000-2016.

Background: A short birth interval is a critical factor that contributes to a large number of maternal and infant mortality in low- and middle-income countries. It is the major cause of maternal and child mortality in Ethiopia. This study aimed to explore the spatiotemporal distribution of short birth intervals in Ethiopia using data from four (2000, 2005, 2011, and 2016) consecutive demographic and health surveys. Methods: A total of 34,930 women were included in four consecutive Ethiopian Demographic and Health Surveys (EDHS). Thus, spatial autocorrelation, hotspot analysis, cluster analysis, and spatial interpolation were carried out for each survey separately to show the geographical and temporal pattern of at-risk areas for short birth intervals in Ethiopia. Finally, the highest proportion of short birth interval risk areas in each survey period was mapped. Geospatial analysis was conducted by using ArcGIS V.10.8 and R version 4.2. Results: The results of the study indicated that the overall proportion of short birth intervals of women in Ethiopia was highest in 2000 (47.5%), 2005 (46.4%), 2011 (44.7%), and the lowest in 2016 (44.0%). The values for Global Moran's I (MI = 0.177665 p = 0.0016, MI = 0.2024, p = 0.001, MI = 0.10023, p = 0.002, and MI = 0.764, p = 0.008) showed that the presence of significant short birth interval clustering in Ethiopian administrative zones in 2000, 2005, 2011, and 2016, respectively. The hotspot areas for short birth intervals were consistently observed in the zones in the Somali Region and the zones in the Harari Region for all the EDHS years. In addition, the survival status of the index child, residence, breastfeeding practice, religion, and the spatial variable (Si) were significantly associated with the short birth interval of women in all the EDHS years. Conclusion: Spatial distribution of short birth intervals differs across Ethiopian administrative zones. Survival status of the index child being dead, rural residential, and no breastfeeding practice are the risk factors for short birth intervals of women that increase the risk of a short birth interval among women in all the EDHS years. Therefore, the hotspot areas and indicators need interventions to decrease the short birth interval of women.

Peri-Operative Inflammatory Cytokines in Plasma of the Elderly Correlate in Prospective Study with Postoperative Changes in Cognitive Test Scores.

Increasingly, postoperative cognitive dysfunction (POCD) is recognized as a complication after surgery in the elderly; but it's etiology remains unclear. Here we examine changes in cytokine levels during both the pre-operative and postoperative period, comparing them with long term variation in cognitive test scores. Forty-one patients aged 65 and older undergoing major surgery with general anesthesia were recruited after written consent in this IRB approved study. Thirty went on to complete this prospective, non-interven-tional and non-randomized study. Plasma levels of cytokines Il-6, Il-8, Il-10, and TNF were determined using ELISA with MILLIPLEX Multi-Analyte Profiling (Billerica, MA). All subjects had neurocognitive tests pre-operatively and 6 months post-surgery, including Paragraph Recall Immediate and Delayed, Digit Span Forward (DSF) and Backward (DSB), and Trail Making A and B. Spearman's Rho and repeated measure rank analysis were used to examine the dependence of z score changes in cognitive tests (baseline versus 6 months) as a function of 3 cytokine time points (presurgical, post anesthesia care unit (PACU), and post-operative day one (POD1)). A greater increase in PACU inflammatory burden correlated with a greater decline in performance on the DSB (IL6, IL8; r>-0.560; p<= 0.008). DSF changes correlated slightly better with pre-surgical cytokines, declining more with higher cytokines (IL6, r= -0.551, p=0.002; IL8, -0.468, 0.009). TNF, examining all 3 values, changed only slightly postoperatively, but still correlated with a decline in DSB (p=0.014). Thus, cognitive performance, over 6 months post surgery, declines with elevated perioperative inflammation. Specific cytokines at specific perioperative times may impact specific cognitive functions, serving as diagnostics as well as contributing causation.

Surgery in the Horn of Africa: a 1-year experience of an American-sponsored surgical residency in Eritrea.

OBJECTIVE: To describe the 1-year experience of a unique postgraduate medical education program set in Eritrea, a recently war-torn country. DESIGN: The Partnership for Eritrea, a cooperative between The George Washington University Medical Center, Physicians for Peace, and the Eritrean Ministry of Health, formed a surgical residency program, launched January 2, 2008, in Asmara, Eritrea, to train native Eritrean surgeons. No prior residency program (to our knowledge) had existed in Eritrea. SETTING: Eritrea, a country in the Horn of Africa. PATIENTS: Five Eritrean physicians participated in the surgical residency. MAIN OUTCOME MEASURES: The number of operations performed, length of stay, antibiotic use, and intravenous fluid use. RESULTS: The number of operations increased and resource use decreased because of improved and standardized clinical management. CONCLUSIONS: The Partnership for Eritrea established a general surgical residency program that improved clinical care in a resource-poor country that previously had lacked postgraduate training. The program experience suggests a model that can be reproduced in other developing countries.

A snapshot of the biodiversity and clustering of Mycobacterium tuberculosis in Oman using spoligotyping.

SETTINGS: National Tuberculosis Reference Laboratory, Central Public Health Laboratory, Ministry of Health, Oman. OBJECTIVE: To use spoligotyping to explore the genetic population structure and clustering of Mycobacterium tuberculosis isolates among nationals and immigrants in Oman. METHODS: Using spoligotyping, we characterised all available isolates from 2007, and randomly selected isolates from 2005 and 2006. A total of 312 clinical isolates from the same number of patients diagnosed with tuberculosis (TB) in 2005-2007 were included in the study. RESULTS: Of 312 isolates, 69% were in clusters ranging from 2 to 38 isolates. The proportion of clustering was 58% among 2005-2006 samples and 67% among 2007 samples, with higher clustering among Omanis than among immigrants. The study showed that M. tuberculosis Indian family lineages, CAS1_Delhi, CAS and EAI5 were the predominant strains. Around 50% of the immigrants shared strains with Omanis. Twelve of the 19 INH-monoresistant strains and the two multidrug-resistant strains were in clusters (P = 0.81). CONCLUSION: This study demonstrates the predominance in Oman of the strain family commonly found on the Indian sub-continent. A high proportion of immigrant strains were in the same clusters as Omani strains. To better ascertain the transmission dynamics of M. tuberculosis, we recommend that stringent molecular and conventional epidemiological methods be applied.

Evaluation of seven tests for the rapid detection of multidrug-resistant tuberculosis in Uganda.

SETTINGS: National Tuberculosis (TB) Reference Laboratory and Department of Medical Microbiology, College of Health Sciences, Makerere University, Kampala, Uganda. OBJECTIVE: To evaluate head-to-head rapid tests for drug susceptibility testing (DST) of Mycobacterium tuberculosis against rifampicin (RMP) and isoniazid (INH) in a resource-limited setting. METHODS: Thirty-one well-characterised strains of M. tuberculosis were tested with the nitrate reductase assay (NRA), microscopic observation drug susceptibility (MODS), MGIT 960 (Mycobacterium Growth Indicator Tube 960), Genotype MTBDRplus, Alamar blue, MTT and resazurin assays. The proportion method on Löwenstein-Jensen medium was used as the reference test. RESULTS: NRA correctly identified the resistant strains, with 100% sensitivity and specificity. MGIT 960 detected all multidrug-resistant strains but missed one RMP-monoresistant strain. Genotype MTBDRplus detected all RMP-resistant strains, but the sensitivity for detection of INH resistance was lower (88%). Sensitivity and specificity ranged from 86% to 100% for MODS and from 57% to 100% for the Alamar blue, MTT and resazurin assays. Test results were obtained within 2-14 days. CONCLUSION: In the study setting, NRA, MGIT 960 and Genotype MTBDRplus gave excellent detection of multidrug-resistant tuberculosis, with significantly shorter time to results compared to conventional testing.

Results of the external quality assessment of Mycobacterium tuberculosis drug susceptibility testing in Russia, 2005-2007.

SETTING: External quality assessment (EQA) of Mycobacterium tuberculosis drug susceptibility testing (DST) in bacteriological tuberculosis (TB) laboratories in the Russian Federation. OBJECTIVE: To improve the EQA of DST of first-line anti-tuberculosis drugs using proficiency testing in the Russian Federation. METHOD: Three rounds of DST proficiency testing using Mycobacterium tuberculosis isolates provided by the Swedish Institute for Infectious Disease Control, a World Health Organization Supranational Reference Laboratory (SRL). In total, 42 TB laboratories in the Russian civilian and prison sectors participated in at least one round of proficiency testing, and 17 laboratories participated in all three rounds. RESULTS: Ninety-seven per cent (87/89) of reports were received for the three rounds: 67% of laboratories in the first round and 86% of laboratories in the second round demonstrated >or=95% accuracy for isoniazid, and respectively 72% and 80% of laboratories in the first and second rounds reported >or=95% accuracy for rifampicin. CONCLUSION: Coordination with the SRL network resulted in the introduction of 90 well-characterised strains for EQA in the Russian Federation. Successive rounds of DST proficiency testing have helped to identify highly proficient laboratories that will be used as expert laboratories for proficiency testing in the future.

Treatment and survival outcome for molecular breast cancer subtypes in black women.

OBJECTIVE: To analyze whether the local-regional surgical treatments (breast-conserving therapy, mastectomy) resulted in different overall survival, distant metastasis-free survival, and locoregional recurrence-free survival rates for the various molecular breast cancer subtypes. SUMMARY BACKGROUND DATA: Molecular gene expression profiling has been proposed as a new classification and prognostication system for breast cancer. Current recommendation for local-regional treatment of breast cancer is based on traditional clinicopathologic variables. METHODS: Retrospective analysis of 372 breast cancer cases with assessable immunohistochemical data for ER, PR, and Her-2/neu receptor status, diagnosed from 1998 to 2005. Molecular subtypes analyzed were luminal A, luminal B, basal like, and Her-2/neu. RESULTS: No substantial difference was noted in overall survival, and locoregional recurrence rate between the local-regional treatment modalities as a function of the molecular breast cancer subtypes. The basal cell-like subtype was an independent predictor of a poorer overall survival (hazard ratio [HR] = 2.52, 95% confidence interval [CI] 1.28-4.97, P < 0.01) and a shorter distant metastasis-free survival time (HR = 3.61, 95% CI 1.27-10.2, P < 0.01), and showed a tendency toward statistical significance as an independent predictor of locoregional recurrence (HR = 3.57, 95% CI 0.93-13.6, P = 0.06). CONCLUSIONS: The basal cell-like subtype is associated with a worse prognosis, a higher incidence of distant metastasis, and may be more prone to local recurrence when managed with breast-conserving therapy.

Basal cell-like (triple-negative) breast cancer, a predictor of distant metastasis in African American women.

BACKGROUND: The aim of this study was to evaluate the prognostic significance of the basal cell-like molecular breast cancer subtype with respect to locoregional recurrence and distant metastasis in African American women treated for breast cancer. METHODS: A retrospective analysis was performed of the tumor registry database for all African American women diagnosed and treated for breast cancer from 1998 to 2005 who had assessable data for all 3 markers: estrogen, progesterone, and Her-2/neu. RESULTS: A total of 372 patients were included in our study sample. Of these, 22 (6.1%) had locoregional recurrence, 35 (9.8%) had distant metastasis, and 301 (84.1%) had no evidence of breast tumor recurrence. The median follow-up time was 36 months. Compared with the other molecular subtypes the basal cell-like subtype showed a statistically significant association to distant metastasis: 15 (42.9%) vs 13 (37.1%), 4 (11.4%), and 3 (8.6%) (P < .001), respectively, for luminal A, Her-2/neu, and luminal B subtypes. The basal cell-like subtype was an independent predictor of distant metastasis (odds ratio, 5.8; 95% confidence interval, 1.5-22.0, P = .009). The molecular subtypes showed no statistically significant difference with respect to locoregional treatment administered and tumor stage at time of diagnosis. CONCLUSIONS: The basal cell-like molecular breast cancer subtype is an independent predictor of distant metastasis in African American women.

Molecular breast cancer subtypes in premenopausal and postmenopausal African-American women: age-specific prevalence and survival.

BACKGROUND: Breast cancer is currently regarded as a heterogeneous disease classified into various molecular subtypes using gene expression analysis. These molecular subtypes include: basal cell-like, Her-2/neu, luminal A, and luminal B. OBJECTIVES: To analyze the prevalence and clinicopathologic associations for molecular breast cancer subtypes in premenopausal and postmenopausal African-American women. DESIGN: A retrospective analysis of all African-American women diagnosed with breast cancer from 1998 to 2005, who had assessable data for ER, PR, and Her-2/neu status. Molecular subtype classification was done based on immunohistochemical surrogates for ER, PR, and Her-2/neu status obtained from Howard University tumor registry for each patient. The molecular subtypes were defined as: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), basal-like (ER-, PR-, HER2-), and Her-2/neu (ER-, PR-, and HER2+). OUTCOME MEASURES: We analyzed the prevalence of molecular breast cancer subtypes in a population of African-American women and determined their associations with patient demographics and clinicopathologic variables: node status, tumor size, histological grade, p53 mutation status, and breast cancer-specific survival. RESULTS: The luminal A subtype was the most prevalent in our study sample (55.4%) compared with (11.8%) luminal B, (21.2%) basal cell-like, and (11.6%) Her-2/neu subtypes. The molecular subtypes did not differ by menopausal status. However, when stratified into age-specific groups, the basal cell-like subtype (57.1%) was the most prevalent in the age group <35 y compared with luminal A, luminal B, and Her-2/neu subtypes at 25.0%, 14.3%, and 3.6%, respectively. The basal cell-like subtype also showed an age-specific bimodal distribution with a peak in the <35 y and 51 to 65 y age groups. The basal cell-like and the Her-2/neu subtypes showed an increased association with clinicopathologic variables portending a more aggressive clinical course when compared with luminal A subtype. A paradoxical inverse relationship between the expression of p53 and Bcl-2 protooncoprotein was noted in the molecular subtypes. Breast cancer-specific survival differed significantly among the molecular subtypes (P < 0.04), with the basal cell-like and Her-2/neu subtypes having the poorest outcome. CONCLUSIONS: The high prevalence of the basal cell-like subtype in the young premenopausal African-American women aged <35 y could be a contributory factor to the poorer prognosis of breast cancer observed in this cohort of patients.

Molecular breast cancer subtypes in premenopausal African-American women, tumor biologic factors and clinical outcome.

INTRODUCTION: Breast cancer is currently viewed as a heterogeneous disease made up of various subtypes, with distinct differences in prognosis. Our goal was to study the distribution and to characterize the clinical and biological factors that influence the behavior and clinical management of the different molecular breast cancer subtypes in premenopausal African-American women. METHODS: A retrospective analysis of Howard University Hospital tumor registry, for all premenopausal African-American women aged less than 50 years, diagnosed with breast cancer from 1998-2005, was performed. RESULTS: The luminal A subtype was the most prevalent (50.0%), vs basal-cell-like (23.2%), luminal B (14.1%), and HER-2/neu (12.7%). However when stratified by age groups, results showed that in the age group <35 years the basal-cell-like subtype was the most prevalent (55.6%), vs 25.9%, 14.8%, and 5.6% for luminal A, luminal B, and HER-2/neu subtypes, respectively (P < .000). P53 mutation was more prevalent in the basal-cell-like subtype compared to luminal A (48.0% vs 18.6%, P < .01). The expression of the Bcl-2 gene differed by subtype, with the luminal A and luminal B subtypes more likely to overexpress the Bcl-2 gene (89.1% luminal A, 80.0% luminal B vs 47.6% basal-cell-like and 40.0% HER-2/neu, P < .000). Though not statistically significant, HER-2/neu and basal-cell-like subtypes had the shortest survival time (P < .31). CONCLUSION: The high prevalence of the basal-cell-like subtype in young premenopausal African-American women aged <35 years may contribute to the poorer prognosis observed in this cohort of African-American women.

Nasal boost with adjuvanted heat-killed BCG or arabinomannan-protein conjugate improves primary BCG-induced protection in C57BL/6 mice.

Today it is generally accepted that the Bacillus Calmette-Guerin (BCG) vaccine protects against childhood tuberculosis (TB) but this immunity wanes with age, resulting in insufficient protection against adult pulmonary TB. Hence, one possible strategy to improve the protective efficacy of the BCG vaccine would be to boost in adulthood. In this study, using the mouse model, we evaluated the ability of two new TB vaccine candidates, heat-killed BCG (H-kBCG) and arabinomannan-tetanus toxoid conjugate (AM-TT), given intransally in a novel Eurocine adjuvant, to boost a primary BCG-induced immune response and to improve protection. Young C57BL/6 mice were vaccinated with conventional BCG and, 6 months later, boosted intranasally with adjuvanted H-kBCG or AM-TT, or subcutaneously with BCG. Ten weeks after the booster, mice were challenged intravenously with M. tuberculosis (Mtb) strain H37Rv. In spleens, there was a significant reduction of cfu counts in mice boosted with either H-kBCG or AM-TT vaccines compared to the non-boosted BCG-vaccinated mice. None of the boosting regimens significantly reduced bacterial loads in lungs, compared to non-boosted BCG vaccination. However, the extent of granulomatous inflammation was significantly reduced in the lungs of mice that received two of the booster vaccines (AM-TT and conventional BCG), as compared with sham-vaccinated mice. All boosted groups, except for mice boosted with the AM-TT vaccine, responded with a proliferation of spleen T cells and gamma interferon production comparable to that induced by a single BCG vaccination.

A mycobacterial lipoarabinomannan specific monoclonal antibody and its F(ab') fragment prolong survival of mice infected with Mycobacterium tuberculosis.

Lipoarabinomannan (LAM) is a major structural carbohydrate antigen of the outer surface of Mycobacterium tuberculosis. High antibody titres against LAM are often seen in active tuberculosis (TB). The role of such LAM-specific antibodies in the immune response against TB is unknown. Here we have investigated a monoclonal antibody (MoAb) SMITB14 of IgG1 subclass and its corresponding F(ab')(2) fragment directed against LAM from M. tuberculosis strain H37Rv. MoAb SMITB14 was shown by immunofluorescence to bind to whole cells of the clinical isolate M. tuberculosis strain Harlingen as well as to M. tuberculosis H37Rv. The binding of MoAb SMITB14 to LAM was inhibited by arabinomannan (AM) and oligosaccharides (5.2 kDa) derived from LAM, showing that the MoAb binds specifically to the AM carbohydrate portion of LAM. In passive protection experiments BALB/c mice were infected intravenously with M. tuberculosis Harlingen. MoAb SMITB14 was added intravenously either prior to, or together with, the bacteria. The antibody proved to be protective against the M. tuberculosis infection in terms of a dose-dependent reduction in bacterial load in spleens and lungs, reduced weight loss and, most importantly, increased long-term survival.

Immunization with heat-killed Mycobacterium bovis bacille Calmette-Guerin (BCG) in Eurocine L3 adjuvant protects against tuberculosis.

The current live attenuated vaccine against tuberculosis, BCG, poses a risk of disseminated infections in immunocompromised subjects. Therefore, in this study we compared the protective effect of a heat-killed bacille Calmette-Guerin (H-kBCG) vaccine given in a new adjuvant (Eurocine L3) with the protection provided by the conventional live attenuated BCG vaccine in mice (C57BL/6 and BALB/c) challenged with virulent Mycobacterium tuberculosis (strain Harlingen). The H-kBCG vaccine alone, in accordance with earlier studies, did not give any or only gave slight protection compared to sham-vaccinated controls. However, the same vaccine given with Eurocine L3 adjuvant, either formulated as a suspension or as an emulsion, afforded significant levels of protection. This protection was at least as good as that of the control live attenuated BCG vaccine. The Eurocine L3 adjuvant is approved for human use as a nasal vaccine adjuvant and a successful phase I trial with nasal immunization with diphtheria vaccine has recently been performed in Sweden. Here we show that, in mice, intranasal priming with H-kBCG in Eurocine L3 adjuvant followed by intranasal booster resulted in the same level of protection as subcutaneous priming followed by intranasal booster. All H-kBCG formulations in the Eurocine L3 adjuvant elicited mycobacterial antigen-specific serum IgG and IFN gamma responses. In general, among the different vaccine formulation(s) in the Eurocine L3 adjuvant those that produced a relatively high Th2 response, as measured by IgG1/IgG2a ratio and IFN gamma production in vitro, were the most protective. In conclusion, H-kBCG in Eurocine L3 adjuvant could represent a safe and a more stable alternative to the conventional live BCG vaccine.

Schistosome transmission, water-resource development and altitude in northern Ethiopia.

Schistosomiasis continues to be a major public-health problem, not least in association with water-resource developments. The impact of microdam construction in the northern Ethiopian highlands, in relation to possible increased risks of Schistosoma mansoni infection, has now been assessed. The results of incidence studies, carried out on 473 individuals sampled across eight microdam sites at altitudes of 1800-2225 m above sea level, indicated an overall annual incidence of 0.20 infections/person at risk. A multivariate Poisson regression model showed altitude and sex to be significant risk factors for infection, whereas proximity to a microdam was not significant, except possibly at very high altitudes. It was concluded that altitude was the major factor in this environment and that therefore, at least in terms of public-health planning, microdams should be sited as high as local geography permits.

Increasing the practice of health promotion initiatives by licensed premises.

Licensees of all licensed premises in the Hunter Region of New South Wales, Australia, were offered free services to encourage adoption of health promotion initiatives relating to responsible service of alcohol, environmental tobacco smoke, healthy food choices, breast and cervical cancer prevention, and the prevention of HIV/AIDS. A total of 239 premises participated in the follow-up survey. Increases in prevalence ranged between 11% and 59% for alcohol-related initiatives. The prevalence of smoke-free areas and healthy food choices increased from 32% to 65% and 42% to 96%, respectively, and the provision of cancer prevention information increased from 3% to 59%. Licensed premises represent a particularly challenging sector for health promotion practitioners to work in. The results of this study suggest that the adoption of health promotion initiatives by licensed premises can be increased. A considerable opportunity therefore exists for health promotion practitioners to become more actively involved in facilitating the adoption of such initiatives in this setting.

Rapid diagnosis of tuberculosis by detection of mycobacterial lipoarabinomannan in urine.

There is an urgent need for improved tools for laboratory diagnosis of active tuberculosis (TB). Here, we describe two methods, a catch-up ELISA and a dipstick test based on the detection in urine of lipoarabinomannan (LAM). LAM is a major and specific glycolipid component of the outer mycobacterial cell wall. Preliminary experiments showed that LAM is excreted in the urine of mice injected intraperitoneally with a crude cell wall preparation of Mycobacterium tuberculosis. Both methods were highly sensitive, detecting LAM at concentrations of 1 ng/ml and 5 pg/ml, respectively. Of 15 patients with active TB, all showed intermediate to high levels of LAM in their urine (absorbance values from 0.3 to 1.2, mean 0.74). Only one sample showed an absorbance value below the chosen cut off value of 0.4. All but one of the urine samples from 26 healthy nursing workers exhibited OD value below 0.4 cut off. These methods may prove valuable for rapid and simple diagnosis of TB in particular in developing countries lacking biosafety level 3 (BSL3) facilities.

The cost of integrating hepatitis B virus vaccine into national immunization programmes: a case study from Addis Ababa.

National programmes of hepatitis B virus (HBV) vaccination are recommended by the World Health Organization for all countries. Countries suffering the highest burden of HBV disease are those most needy of universal vaccination, but are frequently of very low income and resources for health care are scarce. The introduction of HBV vaccination would inevitably stretch these resources further even with support of donor agencies. Thus an assessment of the cost-effectiveness of HBV vaccination is desirable to assist in decision making about resource allocation. We describe here a method for estimating the additional costs of introducing HBV vaccination into the Expanded Programme on Immunization (EPI) at a national level. Of fundamental importance is that this method enables costs to be assessed prior to the introduction of vaccination. We illustrate the method using a study carried out at the sub-national level, in the city of Addis Ababa, Ethiopia, but which can be expanded countrywide. The method, in brief, involved the use of a number of questionnaires which could be used to estimate the costs associated with the EPI programme from a large sample of the static clinics as well as from central sources. Since unit costs were collected along with the quantities of resources used and estimates of the capacity used for certain facilities (such as refrigerators), the additional cost of introducing HBV vaccine could be estimated largely by extrapolation of the resources used in vaccinating against diphtheria/pertussis/tetanus vaccine (which, similar to HBV vaccine, requires three doses). The estimation of costs is only part of the information required to make decisions on resource allocation, and should be used in association with measures of the burden of disease due to the infection in the community and effectiveness of the control programme at reducing this burden. The prediction of the latter, based upon a sound epidemiological understanding of the infection, is the subject of a forthcoming paper.

Isoflurane pretreatment ameliorates postischemic neurologic dysfunction and preserves hippocampal Ca2+/calmodulin-dependent protein kinase in a canine cardiac arrest model.

BACKGROUND: Inhalational anesthetics are neuroprotective in rat models of global ischemia. To determine whether isoflurane at a clinically relevant concentration is neuroprotective in a canine model of cardiac arrest, we measured neurologic function and hippocampal Ca2+/calmodulin-dependent protein kinase II (CaMKII) content 20 h after cardiac arrest. METHODS: We tested the neuroprotective effect of 30 min of 1.5% isoflurane exposure before 8 min of global ischemia induced with ventricular fibrillation. Animals were randomized to four groups: control, isoflurane-control, ischemia, and isoflurane-ischemia. After resuscitation and 20 h of intensive care, each animal's neurologic deficit score was determined by two blinded evaluators. The hippocampal content of CaMKII, determined by immunoblotting, was measured by an individual blinded to the treatment groups. CaMKII activity was measured in samples from the cortex, hippocampus, and striatum of animals in each group. RESULTS: Isoflurane-ischemic animals had a median neurologic deficit score of 22.6% compared with 43.8% for the ischemic animals (P < 0.05). Hippocampal levels of the beta-subunit of CaMKII (CaMKIIbeta) were relatively preserved in isoflurane-ischemic animals (68 +/- 4% of control) compared with ischemic animals (48 +/- 2% of control; P < 0.001), although both groups were statistically significantly lower than control (P < 0. 001 ischemia vs. control and P < 0.05 isoflurane-ischemia vs. control). CONCLUSIONS: Isoflurane is an effective neuroprotective drug in a canine cardiac arrest model in terms of both functional and biochemical criteria.

Household risk factors for malaria among children in the Ethiopian highlands.

Malaria transmission varies from village to village and even from family to family in the same village. The current study was conducted in northern Ethiopia to identify risk factors responsible for such variations in a hypoendemic highland malaria setting: 2114 children aged < 10 years living in 6 villages situated close to small dams at altitudes from 1775 to 2175 m were monitored. Monthly malaria incidence was determined 4 times over a 1-year period during 1997. Incidence results were then analysed by 14 individual and household factors using Poisson multivariate regression. Among 14 factors analysed, use of irrigated land (rate ratio[RR] = 2.68, 95% CI 1.64-4.38), earth roof (RR = 2.15, 95% CI 1.31-3.52), animals sleeping in the house (RR = 1.92, 95% CI 1.29-2.85), windows (RR = 1.84, 95% CI 1.30-2.63), open eaves (RR = 1.85, 95% CI 1.19-2.88), no separate kitchen (RR = 1.57, 95% CI 1.10-2.23), and 1 sleeping room (RR = 1.52, 95% CI 1.05-2.20), were significantly associated with malaria. The proportion of infection among children exposed to one or no risk factor was 2.1%, increasing with the number of risk factors and reaching 29.4% with 5 or more. Further studies are needed to confirm the importance of particular risk factors, possibly leading to simple health education and control measures that could become part of routine control programmes, implemented with inter-sectoral collaboration.

Incidence of malaria among children living near dams in northern Ethiopia: community based incidence survey.

OBJECTIVE: To assess the impact of construction of microdams on the incidence of malaria in nearby communities in terms of possibly increasing peak incidence and prolonging transmission. DESIGN: Four quarterly cycles of malaria incidence surveys, each taking 30 days, undertaken in eight at risk communities close to dams paired with eight control villages at similar altitudes but beyond flight range of mosquitoes. SETTING: Tigray region in northern Ethiopia at altitudes of 1800 to 2225 m. SUBJECTS: About 7000 children under 10 years living in villages within 3 km of microdams and in control villages 8-10 km distant. MAIN OUTCOME MEASURES: Incidence of malaria in both communities. RESULTS: Overall incidence of malaria for the villages close to dams was 14.0 episodes/1000 child months at risk compared with 1.9 in the control villages-a sevenfold ratio. Incidence was significantly higher in both communities at altitudes below 1900 m. CONCLUSIONS: There is a need for attention to be given to health issues in the implementation of ecological and environmental development programmes, specifically for appropriate malaria control measures to counteract the increased risks near these dams.

PIP: This paper assesses the impact of microdam construction on the incidence of malaria in nearby communities in Tigray, Ethiopia, in terms of possibly increasing peak incidence and prolonging transmission. Four quarterly cycles of malaria incidence surveys, each taking 30 days, were undertaken in eight at-risk communities close to dams paired with eight control villages at similar altitudes but beyond the flight range of mosquitoes. Samples included about 700 children under 10 years of age living in villages within 3 km of microdams and in control villages 8-10 km distant. Results showed that the overall incidence of malaria for the villages close to the dams was 14.0 episodes/1000 child-months at risk compared with 1.9 in the control villages. Incidence was significantly higher in both communities at altitudes below 1900 m. This paper suggests the need to address health issues in the implementation of ecological and environmental development programs, specifically regarding appropriate malaria control measures to counteract the increased risks near these dams.