Biomass fuel use and acute respiratory infection among children younger than 5 years in Ethiopia: a systematic review and meta-analysis.

OBJECTIVES: The objective of this study was to estimate the magnitude of acute respiratory infection (ARI) among children younger than 5 years (under-five children) and its association with biomass fuel use for domestic purposes and other behavioural and housing characteristics in Ethiopia. STUDY DESIGN: Systematic review and meta-analysis. METHODS: PubMed, Google Scholar, MEDLINE and the Cochrane Library were systematically searched (using the Preferred Items for Systematic Review and Meta-analysis guideline) for studies that reported an association between biomass fuel use for domestic purposes and ARI. Grey literature and other sources of unpublished information, which were subjected to the same extraction methods and quality appraisal as published studies, were also identified. A meta-analysis was performed to combine the quantitative measures from eligible individual studies into a summary estimate. Quality assessment was conducted using the modified Newcastle-Ottawa Scale quality assessment tool for cross-sectional and case-control studies. Funnel and Doi plots were used to detect potential publication bias. Statistical analyses were performed using Comprehensive Meta-Analysis and MetaXL, version 5.3, software. RESULTS: A total of 21 (18 cross-sectional and 3 case-control) eligible studies with their combined 30,013 participants were reviewed. The overall pooled prevalence of ARI among under-five children in households where biomass fuel was the main source of energy was estimated to be 22% (95% confidence interval [CI]: 17-29). In the subgroup analysis by area of residence, the highest prevalence was found in urban regions 26% (95% CI: 24-28). Based on the preceding 2 weeks before the interview, a significant association was found between biomass fuel use and ARI (odds ratio [OR] = 2.6, 95% CI: 2.05-3.30). In addition to biomass fuel use, being female (OR = 1.57, 95% CI: 1.06-2.33), absence of a window in the kitchen (OR = 2.89, 95% CI: 2.11-3.96), being carried on the back or in lap during cooking (OR = 2.76, 95% CI: 1.96-3.89) and non-separated kitchen from the main house (OR = 1.99, 95% CI: 1.49-2.68) were associated with ARI. CONCLUSIONS: Based on the results of this review, ARI among under-five children remains high. The present study also revealed that ARI is associated with biomass fuel use, child's gender, absence of a window in the kitchen, non-separated kitchen and carrying the child while cooking. Improved solid fuel stoves, advanced combustion designs, windows or chimneys, separating the kitchen from the main house are all measures required to reduce ARI in under-five children. SYSTEMATIC REVIEW REGISTRATION: The review has been registered with PROSPERO (registration number CRD42020181372).

Loss-of-Function GRHL3 Variants Detected in African Patients with Isolated Cleft Palate.

In contrast to the progress that has been made toward understanding the genetic etiology of cleft lip with or without cleft palate, relatively little is known about the genetic etiology for cleft palate only (CPO). A common coding variant of grainyhead like transcription factor 3 ( GRHL3) was recently shown to be associated with risk for CPO in Europeans. Mutations in this gene were also reported in families with Van der Woude syndrome. To identify rare mutations in GRHL3 that might explain the missing heritability for CPO, we sequenced GRHL3 in cases of CPO from Africa. We recruited participants from Ghana, Ethiopia, and Nigeria. This cohort included case-parent trios, cases and other family members, as well as controls. We sequenced exons of this gene in DNA from a total of 134 nonsyndromic cases. When possible, we sequenced them in parents to identify de novo mutations. Five novel mutations were identified: 2 missense (c.497C>A; p.Pro166His and c.1229A>G; p.Asp410Gly), 1 splice site (c.1282A>C p.Ser428Arg), 1 frameshift (c.470delC; p.Gly158Alafster55), and 1 nonsense (c.1677C>A; p.Tyr559Ter). These mutations were absent from 270 sequenced controls and from all public exome and whole genome databases, including the 1000 Genomes database (which includes data from Africa). However, 4 of the 5 mutations were present in unaffected mothers, indicating that their penetrance is incomplete. Interestingly, 1 mutation damaged a predicted sumoylation site, and another disrupted a predicted CK1 phosphorylation site. Overexpression assays in zebrafish and reporter assays in vitro indicated that 4 variants were functionally null or hypomorphic, while 1 was dominant negative. This study provides evidence that, as in Caucasian populations, mutations in GRHL3 contribute to the risk of nonsyndromic CPO in the African population.

Mortality and Disability-Adjusted Life-Years (Dalys) for Common Neglected Tropical Diseases in Ethiopia, 1990-2015: Evidence from the Global Burden of Disease Study 2015.

INTRODUCTION: Neglected tropical diseases (NTDs) are important public health problems in Ethiopia. In 2013, the Federal Ministry of Health (FMOH) has launched a national NTD master plan to eliminate major NTDs of public health importance by 2020. Benchmarking the current status of NTDs in the country is important to monitor and evaluate the progress in the implementation of interventions and their impacts. Therefore, this study aims to assess the trends of mortality and Disability-adjusted Life-Years (DALY) for the priority NTDs over the last 25 years. METHODS: We used the Global Burden of Disease (GBD) 2015 estimates for this study. The GBD 2015 data source for cause of death and DALY estimation included verbal autopsy (VA), Demographic and Health Surveys (DHS), and other disease specific surveys, Ministry of Health reports submitted to United Nations (UN) agencies and published scientific articles. Cause of Death Ensemble modeling (CODEm) and/or natural history models were used to estimate NTDs mortality rates. DALY were estimated as the sum of Years of Life Lost (YLL) due to premature mortality and Years Lived with Disability (YLD). RESULTS: All NTDs caused an estimated of 6,293 deaths (95% uncertainty interval (UI): 3699-10,080) in 1990 and 3,593 deaths (95% UI: 2051 - 6178) in 2015, a 43% reduction over the 25 years. Age-standardized mortality rates due to schistosomiasis, STH and leshmaniasis have declined by 91.3%, 73.5% and 21.6% respectively between 1990 to 2015. The number of DALYs due to all NTDs has declined from 814.4 thousand (95% UI: 548 thousand-1.2million) in 1990 to 579.5 thousand (95%UI: 309.4 thousand-1.3 million) in 2015. Age-standardized DALY rates due to all NTDs declined by 30.7%, from 17.6 per 1000(95%UI: 12.5-26.5) in 1990 to 12.2 per 1000(95%UI: 6.5 - 27.4) in 2015. Age-standardized DALY rate for trachoma declined from 92.7 per 100,000(95% UI: 63.2 - 128.4) in 1990 to 41.2 per 100,000(95%UI: 27.4-59.2) in 2015, a 55.6% reduction between 1990 and 2015. Age-standardized DALY rates for onchocerciasis, schistosomiasis and lymphiaticfilariasis decreased by 66.2%, 29.4% and 12.5% respectively between 1990 and 2015. DALY rate for ascariasis fell by 56.8% over the past 25 years. CONCLUSIONS: Ethiopia has made a remarkable progress in reducing the DALY rates for most of the NTDs over the last 25 years. The rapid scale of interventions and broader system strengthening may have a lasting impact on achieving the 2020 goal of elimination of most of NTDs. Ethiopia should strengthen the coverage of integrated interventions of NTD through proper coordination with other health programs and sectors and community participation to eliminate NTDs by 2020.

Malnutrition in Healthy Individuals Results in Increased Mixed Cytokine Profiles, Altered Neutrophil Subsets and Function.

Malnutrition is commonly associated with increased infectious disease susceptibility and severity. Whereas malnutrition might enhance the incidence of disease as well as its severity, active infection can in turn exacerbate malnutrition. Therefore, in a malnourished individual suffering from a severe infection, it is not possible to determine the contribution of the pre-existing malnutrition and/or the infection itself to increased disease severity. In the current study we focussed on two groups of malnourished, but otherwise healthy individuals: moderately malnourished (BMI: 18.4-16.5) and severely malnourished (BMI <16.5) and compared several immune parameters with those of individuals with a normal BMI (≥18.5). Our results show a similar haematological profile in all three groups, as well as a similar ratio of CD4+ and CD8+ T cells. We found significant correlations between low BMI and increased levels of T helper (Th) 1 (Interferon (IFN)-γ, (interleukin (IL)-2, IL-12), Th2 (IL-4, IL-5, IL-13), as well as IL-10, IL-33 and tumor necrosis factor-α, but not IL-8 or C reactive protein. The activities of arginase, an enzyme associated with immunosuppression, were similar in plasma, peripheral blood mononuclear cells (PBMC) and neutrophils from all groups and no differences in the expression levels of CD3ζ, a marker of T cell activation, were observed in CD4+ and CD8+T cells. Furthermore, whereas the capacity of neutrophils from the malnourished groups to phagocytose particles was not impaired, their capacity to produce reactive oxygen species was impaired. Finally we evaluated the frequency of a subpopulation of low-density neutrophils and show that they are significantly increased in the malnourished individuals. These differences were more pronounced in the severely malnourished group. In summary, our results show that even in the absence of apparent infections, healthy malnourished individuals display dysfunctional immune responses that might contribute to increased susceptibility and severity to infectious diseases.

Validation and Clinical Evaluation of a Novel Method To Measure Miltefosine in Leishmaniasis Patients Using Dried Blood Spot Sample Collection.

To facilitate future pharmacokinetic studies of combination treatments against leishmaniasis in remote regions in which the disease is endemic, a simple cheap sampling method is required for miltefosine quantification. The aims of this study were to validate a liquid chromatography-tandem mass spectrometry method to quantify miltefosine in dried blood spot (DBS) samples and to validate its use with Ethiopian patients with visceral leishmaniasis (VL). Since hematocrit (Ht) levels are typically severely decreased in VL patients, returning to normal during treatment, the method was evaluated over a range of clinically relevant Ht values. Miltefosine was extracted from DBS samples using a simple method of pretreatment with methanol, resulting in >97% recovery. The method was validated over a calibration range of 10 to 2,000 ng/ml, and accuracy and precision were within ±11.2% and ≤7.0% (≤19.1% at the lower limit of quantification), respectively. The method was accurate and precise for blood spot volumes between 10 and 30 µl and for Ht levels of 20 to 35%, although a linear effect of Ht levels on miltefosine quantification was observed in the bioanalytical validation. DBS samples were stable for at least 162 days at 37°C. Clinical validation of the method using paired DBS and plasma samples from 16 VL patients showed a median observed DBS/plasma miltefosine concentration ratio of 0.99, with good correlation (Pearson'sr= 0.946). Correcting for patient-specific Ht levels did not further improve the concordance between the sampling methods. This successfully validated method to quantify miltefosine in DBS samples was demonstrated to be a valid and practical alternative to venous blood sampling that can be applied in future miltefosine pharmacokinetic studies with leishmaniasis patients, without Ht correction.

Specific antibody responses as indicators of treatment efficacy for visceral leishmaniasis.

Acute visceral leishmaniasis (VL) is caused by infection with parasites of the Leishmania donovani complex and may be fatal if not treated. Early diagnosis and efficacious treatment are the keys to effective VL management and control. Novel regimens are being developed to overcome limitations in VL treatment options, which are currently restricted by high costs, severe systemic side effects, and unresponsiveness. Although simple and accurate serological tests are available to help confirm VL, none are suitable to monitor treatment efficacy and cure. Here, we confirm that serum antibody responses to the diagnostic antigens rK39 and rK28 are unaltered by treatment, but demonstrate that antibodies produced against two antigens, rK26 and rK18, can be used as an indirect measure of parasite clearance. The levels of anti-rK18 and -rK26 antibodies were high in patients at initial diagnosis but declined in patients treated with either SSG (Ethiopia) or AmBisome (Bangladesh). Taken together, we propose that serological tests which measure antibodies to rK26 and rK18 merit consideration as potential markers of treatment success and cure.

Susceptibility of clinical isolates of Leishmania aethiopica to miltefosine, paromomycin, amphotericin B and sodium stibogluconate using amastigote-macrophage in vitro model.

Cutaneous Leishmaniasis (CL) caused by Leishmania aethiopica is a public health and social problem with a sequel of severe and mutilating skin lesions. It is manifested in three forms: localized CL (LCL), mucosal CL (MCL) and diffuse CL (DCL). Unresponsiveness to sodium stibogluconate (Sb(V)) is common in Ethiopian CL patients. Using the amastigote-macrophage in vitro model the susceptibility of 24 clinical isolates of L. aethiopica derived from untreated patients was investigated. Eight strains of LCL, 9 of MCL, and 7 of DCL patients together with a reference strain (MHOM/ET/82/117/82) were tested against four antileishmanial drugs: amphotericin B, miltefosine, Sb(V) and paromomycin. In the same order of drugs, IC(50) (µg/ml±SD) values for the 24 strains tested were 0.16±0.18, 5.88±4.79, 10.23±8.12, and 13.63±18.74. The susceptibility threshold of isolates originating from the 3 categories of patients to all 4 drugs was not different (p>0.05). Maximal efficacy was superior for miltefosine across all the strains. Further susceptibility test could validate miltefosine as a potential alternative drug in cases of sodium stibogluconate treatment failure in CL patients.

Antiretroviral therapy abrogates association between arginase activity and HIV disease severity.

Arginase-induced L-arginine deprivation is emerging as a key mechanism for the downregulation of immune responses. We hypothesised that arginase activity increases with disease severity in HIV-seropositive patients. Our results show that peripheral blood mononuclear cells (PBMCs) from 23 HIV-seropositive patients with low CD4(+) T cell counts (≤350 cells/µl) expressed significantly more arginase compared with 21 patients with high CD4(+) T cell counts. Furthermore, we found a significant association between the two principal prognostic markers used to monitor HIV disease (CD4(+) T cell count and plasma viral load) and PBMC arginase activity in antiretroviral therapy naïve patients but not in patients undergoing therapy.

Increased level of arginase activity correlates with disease severity in HIV-seropositive patients.

Infection with human immunodeficiency virus (HIV) results in a chronic infection that progressively impairs the immune system. Although depletion of CD4(+) T cells is frequently used to explain immunosuppression, chronicity of infection and progressive loss of CD4(+) T cells are not sufficient to fully account for immune dysregulation. Arginase-induced l-arginine deprivation is emerging as a key mechanism for the down-regulation of immune responses. Here, we hypothesized that the level of arginase activity increases with disease severity in HIV-seropositive patients. We determined the levels of arginase activity in peripheral blood mononuclear cells from HIV-seropositive patients and uninfected control participants. Our results show that peripheral blood mononuclear cells from HIV-seropositive patients with low CD4(+) T cell counts expressed statistically significantly higher levels of arginase activity, compared with patients with high CD4(+) T cell counts or uninfected control participants. Furthermore, we found a statistically significant correlation between high level of arginase activity and high viral load in HIV-seropositive patients.

A clinical isolate of Leishmania donovani with ITS1 sequence polymorphism as a cause of para-kala-azar dermal leishmaniasis in an Ethiopian human immunodeficiency virus-positive patient on highly active antiretroviral therapy.

The diagnosis of para-kala-azar dermal leishmaniasis (PKDL/VL), either as an immune reconstitution inflammatory syndrome (IRIS)-associated syndrome or as a complication of visceral leishmaniasis (VL) during human immunodeficiency virus (HIV) co-infection in patients with or without highly active antiretroviral therapy, represents a challenge for prompt treatment. The aim of this study was to identify the causative Leishmania species and to clarify whether the post-kala-azar dermal leishmaniasis (PKDL)-like lesions appeared as a result of IRIS or not. A 31-year-old Ethiopian male patient, with stage IV HIV/acquired immune deficiency syndrome (AIDS), was clinically diagnosed with PKDL/VL. He had developed a generalized maculopapular rash on his face after initiation of highly active antiretroviral therapy. The Leishmania isolate obtained from the skin lesions was analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing of the ribosomal DNA internal transcribed spacer 1 (ITS1) and partial coding sequences of the heat shock protein 70 gene (hsp70). Restriction analysis of the ITS1 PCR product gave a unique RFLP pattern not seen before for any Leishmania isolate. Sequencing of both the ITS1 and hsp70 PCR products identified the causative species as Leishmania donovani, and further revealed the existence of five different sequence variants of the ITS1 among the 10 clones sequenced. The results indicate that PKDL/VL resulted from an infection by L. donovani. The sequence variants of ITS1 might be due to the presence of multiple strains/clones or the existence of intragenomic variations in the multicopy ITS1, or a combination of both.

Current Status of Intestinal Schistosomiasis and Soil Transmitted Helminthiasis among Primary School Children in Adwa Town; Northern Ethiopia

Background: Epidemiological baseline information on the prevalence and intensity of parasitic infections in a given locality is a prerequisite for development and evaluation of sound control strategies. Objective: To determine the current status of schistosomiasis and soil-transmitted helminthiasis among primary school children in Adwa Town; northern Ethiopia. Methods: A cross-sectional epidemiological study was carried out in eight primary schools in Adwa Town between October and November 2007. Fecal samples of 386 school children in the age group 7-18 were collected and microscopically examined using the Kato-Katz and formol-ether concentration methods. A questionnaire was used to identify determinants for Schistosoma mansoni and soil-transmitted helminth infections. Results: The most prevalent intestinal parasitic infection among primary school children in Adwa Town as determined by Kato-Katz (58.7) and formol ether concentration (60.6) methods was intestinal schistosomiasis; with an overall intensity of 95.8 eggs per gram of stool. The prevalence of S. mansoni infection was higher in males (70.7) than in females (57); as determined by both methods. Less common parasites observed included Ascaris lumbricoides; hookworm species; Hymenolepis nana; Strongyloides stercoralis; and Entamoeba histolytica/dispar. Conclusion: The residents of Adwa Town represent a high-risk community with respect to intestinal schistosomiasis. Hence; mass praziquantel administration to school-age children and all adults considered to be at risk is required once a year until the level of infection falls below the level of public health importance. There is also a need to supplement chemotherapy with other measures such as environmental sanitation and health education to make the impact of chemotherapy sustainable. [Ethiop. J. Health Dev. 2010;24(3):191-197]

Schistosomiasis Mansoni and Soil-Transmitted Helminthiasis in Bushulo Village; Southern Ethiopia

Background:Schistosomiasis mansoni and soil-transmitted helminthiasis (STHs) are considerable medical and public health problems in Ethiopia. However; information is limited on the epidemiology of these infections in different localities even though it is needed to plan effective prevention and control measures.Objective: This study was designed to determine the prevalence of Schistosoma mansoni and soil-transmitted helminth infections in school children and residents in Bushulo village near Lake Awassa (Hawassa); southern Ethiopia.Methods: Cross-sectional epidemiological and parasitological studies were conducted on schistosomiasis mansoni and STHs in Bushulo village in May and June 2007. A total of 419 participants (353 school children and 66 other residents) were included in the study. The principal investigator interviewed the study subjects about demographic status using structured questionnaires. Moreover; experienced nurse took history and conducted physical examination to assess symptoms and signs related to chronic S. mansoni infection. A single stool sample was collected from each participant and processed using the Kato-Katz technique. Experienced laboratory technician read all slides at Bushulo Health Center. Results: The overall infection rates of schistosomiasis mansoni; trichuriasis; ascariasis and hookworm infection were 73.7; 41.5; 37.2and 28.4; respectively. Other parasitic infections observed were caused by Hymenolepis nana (1.7); Taenia species (1.4); and Enterobius vermicularis (1.4). Children in the age range 10-14 years and those attending at St. Paul's School had higher rates of T. trichiura and S. mansoni; respectively. Intensity of infection was higher for A. lumbricoides in the age range 5-9 years. The overall prevalence of any STHs was 67.3. The rates of single; dual; triple and quadruple infections were 29.6; 32; 20.3and 7.4; respectively. Conclusion: The high prevalence and intensity of schistosomiasis mansoni and soil-transmitted helminthiasis makes periodic deworming programme urgent to reduce morbidity and transmission of helminthiasis in the area. Provisions of sanitary facilities and clean water supply as well as health education are also critically needed to sustain the impact of chemotherapy

Visceral leishmaniasis in Aba-Roba, south-western Ethiopia: prevalence and incidence of active and subclinical infections.

Between August 1997 and February 2005, a prospective study of human visceral leishmaniasis (VL) was undertaken in two villages in the Konso district of south-western Ethiopia, to provide epidemiological indices of subclinical infection and active VL. Six cross-sectional surveys at 6-month intervals (ending in August 2000) were complemented by a single survey in February 2005. The prevalences and incidences of leishmanial infection and active VL, which were determined using leishmanin skin tests (LST), direct agglutination tests (DAT) and parasitological diagnosis, varied spatio-temporally and by age and gender. At baseline, when 1339 individuals were investigated, the overall prevalences of LST positivity, DAT positivity and active VL among the 1232 subjects who had not been treated previously were 30.0%, 5.4% and 0.49%, respectively. During the study, <10% of the subjects found DAT-positive at baseline progressed to active VL (with a mean of about nine cases of subclinical infection for every one of active VL). The median age of an incident VL case was 10.5 years. The highest rates of LST conversion occurred among the subjects aged 5-25 years. A subject who became LST-positive during the study was much less likely to develop active VL than the other subjects.

Lying about facial recognition: an fMRI study.

Novel deception detection techniques have been in creation for centuries. Functional magnetic resonance imaging (fMRI) is a neuroscience technology that non-invasively measures brain activity associated with behavior and cognition. A number of investigators have explored the utilization and efficiency of fMRI in deception detection. In this study, 18 subjects were instructed during an fMRI "line-up" task to either conceal (lie) or reveal (truth) the identities of individuals seen in study sets in order to determine the neural correlates of intentionally misidentifying previously known faces (lying about recognition). A repeated measures ANOVA (lie vs. truth and familiar vs. unfamiliar) and two paired t-tests (familiar vs. unfamiliar and familiar lie vs. familiar truth) revealed areas of activation associated with deception in the right MGF, red nucleus, IFG, SMG, SFG (with ACC), DLPFC, and bilateral precuneus. The areas activated in the present study may be involved in the suppression of truth, working and visuospatial memories, and imagery when providing misleading (deceptive) responses to facial identification prompts in the form of a "line-up".

1H MRS identifies symptomatic and asymptomatic subjects with partial ornithine transcarbamylase deficiency.

OBJECTIVE: To evaluate brain metabolism in subjects with partial ornithine transcarbamylase deficiency (OTCD) utilizing (1)H MRS. METHODS: Single-voxel (1)H MRS was performed on 25 medically-stable adults with partial OTCD, and 22 similarly aged controls. Metabolite concentrations from frontal and parietal white matter (FWM, PWM), frontal gray matter (FGM), posterior cingulate gray matter (PCGM), and thalamus (tha) were compared with controls and IQ, plasma ammonia, glutamine, and disease severity. RESULTS: Cases ranged from 19 to 59 years; average 34 years; controls ranged from 18 to 59 years; average 33 years. IQ scores were lower in cases (full scale 111 vs. 126; performance IQ 106 vs. 117). Decreased myoinositol (mI) in FWM (p=0.005), PWM (p<0.001), PCGM (p=0.003), and tha (p=0.004), identified subjects with OTCD, including asymptomatic heterozygotes. Glutamine (gln) was increased in FWM (p<0.001), PWM (p<0.001), FGM (p=0.002), and PCGM (p=0.001). Disease severity was inversely correlated with [mI] in PWM (r=-0.403; p=0.046) and directly correlated with [gln] in PCGM (r=0.548; p=0.005). N-Acetylaspartate (NAA) was elevated in PWM (p=0.002); choline was decreased in FWM (p=0.001) and tha (p=0.002). There was an inverse relationship between [mI] and [gln] in cases only. Total buffering capacity (measured by [mI/mI+gln] ratio, a measure of total osmolar capacity) was inversely correlated with disease severity in FWM (r=-0.479; p=0.018), PWM (r=-0.458; p=0.021), PCGM (r=-0.567; p=0.003), and tha (r=-0.345; p=0.037). CONCLUSION: Brain metabolism is impaired in partial OTCD. Depletion of mI and total buffering capacity are inversely correlated with disease severity, and serve as biomarkers.

Evaluation of circulating cathodic antigen (CCA) strip for diagnosis of urinary schistosomiasis in Hassoba school children, Afar, Ethiopia.

A total of 206 urine samples collected from Hassoba Elementary schoolchildren, Afar, Ethiopia, a low Schistosoma haematobium endemic setting, was diagnosed to evaluate the performance of CCA strip using double references, urine filtration technique and urinalysis dipstick (Combur 1.0 Test) that detect schistosome eggs and blood in urine, respectively. The former was used as a gold standard reference method. Sensitivity, specificity, positive and negative predictive values for the CCA were 52%, 63.8%, 56.7% and 59% respectively, with reference to urine filtration technique whereas these parameters were 50.4%, 62.4%, 55.6% and 57.5% respectively, with reference to Combur 10 Test. 47 S. haematobium egg-positive children were found negative by CCA strip while 38 egg-negative children were found positive by CCA strip. Moreover, among the pre-tests done in duplicate, inconsistent results were also recorded. Assays were also compared with regard to the cost of equipment and reagents, speed and simplicity of use. Though CCA strip was found to be rapid and could be performed with minimal training, it was found to be expensive (US $ 4.95 per test) to use it for large-scale field use even if its diagnostic value would have been satisfactory. Further development and standardization of the CCA strip are required for its applicability for field use. It is also recommended that its cost per strip should be substantially cut down if it is to be used in poor schistosomiasis endemic countries.

Diagnostic tests for kala-azar: a multi-centre study of the freeze-dried DAT, rK39 strip test and KAtex in East Africa and the Indian subcontinent.

Three diagnostic tests for visceral leishmaniasis (VL), the freeze-dried direct agglutination test (FD-DAT), the rK39 dipstick and a urine latex antigen test (KAtex), were evaluated for use in primary care in East Africa and the Indian subcontinent. Clinical suspects were prospectively recruited and tissue, blood and urine samples were taken. Direct microscopic examination of tissue smear, and FD-DAT, rK39 and KAtex were performed. Sensitivity and specificity with 95% credible intervals were estimated using Bayesian latent class analysis. On the Indian subcontinent both the FD-DAT and the rK39 strip test exceeded the 95% sensitivity and 90% specificity target, but not so in East Africa. Sensitivity of the FD-DAT was high in Ethiopia and Kenya but lower in Sudan, while its specificity was below 90% in Kenya. Sensitivity of the rK39 was below 80% in the three countries, and its specificity was only 70% in Ethiopia. KAtex showed moderate to very low sensitivity in all countries. FD-DAT and rK39 can be recommended for clinical practice on the Indian subcontinent. In East Africa, their clinical use should be carefully monitored. More work is needed to improve existing formats, and to develop better VL diagnostics.

Associations between meat consumption and the prevalence of degenerative arthritis and soft tissue disorders in the adventist health study, California U.S.A.

OBJECTIVE: To examine associations between the prevalence of degenerative arthritis and soft tissue disorders and consumption of meat and other foods among participants in the Adventist Health Study. METHODS: Unconditional logistic regression analysis is used to examine cross-sectional associations, adjusting for the effects of age, smoking, alcohol consumption, body mass index, use of sex hormones and parity. RESULTS: The prevalence of degenerative arthritis and soft tissue disorders was 22.60 percent. Women had a higher prevalence than men and prevalence increased greatly with age. Smoking, higher body mass index, never use of contraceptive pills, and current hormone replacement therapy are associated with a higher prevalence of these disorders on multivariate analysis. Multivariate OR's comparing consumption of meat < 1/week; >or= 1/week; with the reference being no meat, were 1.31(95% CI: 1.21,1.43) and 1.49(1.31, 1.70) in women; and 1.19 (95% CI: 1.05,1.34) and 1.43(1.20, 1.70) in men. Dairy fat and fruit consumption were weakly associated with increased risk. There were protective associations with nut and salad consumption. CONCLUSIONS: Greater meat consumption is associated with a higher prevalence of degenerative arthritis and soft tissue disorders in both male and female subjects of this population, as is hormone replacement therapy in women.

Field evaluation of a fast anti-Leishmania antibody detection assay in Ethiopia.

A fast agglutination screening test (FAST) for the detection of Leishmania antibodies in human serum samples was evaluated under harsh field conditions in northern Ethiopia. Test performance was compared with a standard serological test, namely the direct agglutination test (DAT), and with parasitology. In total, 103 suspected cases were recruited for the study. Based on parasitological examination, 49 patients were confirmed of having visceral leishmaniasis (VL) and the other 54 suspected cases were parasitologically negative. Field evaluation of FAST was possible in blood samples of 89 patients. FAST had 4 false negative results and 13 false positive results. DAT had 2 false negative results and 20 false positive results. A good degree of agreement (86.9%) was observed between FAST and DAT (kappa value 0.73). In this field-based evalauation, the sensitivity and specificity of FAST were found to be 91.1% (95% CI 77.9-97.1) and 70.5% (95% CI 54.6-82.8), respectively, compared with 95.3% (95% CI 82.9-99.2) and 62.3% (95% CI 47.9-74.9) for DAT. FAST had a high predictive value of a negative test, demonstrating that FAST could be utilised to exclude rapidly non-VL patients from a large population of suspects with fever and splenomegaly in endemic areas.

Mapping the potential distribution of Phlebotomus martini and P. orientalis (Diptera: Psychodidae), vectors of kala-azar in East Africa by use of geographic information systems.

The distribution of two principal vectors of kala-azar in East Africa, Phlebotomus martini and Phlebotomus orientalis were analysed using geographic information system (GIS) based on (1) earth observing satellite sensor data: Normalized Difference Vegetation Index (NDVI) and midday Land Surface Temperature (LST) derived from advanced very high resolution radiometer (AVHRR) of the global land 1km project of United States Geological Survey (USGS), (2) agroclimatic data from the FAO Crop Production System Zone (CPSZ) of the Intergovernmental Authority on Development (IGAD) sub-region, and (3) the FAO 1998 soils digital map for the IGAD sub-region. The aim was to produce a predictive risk model for the two vectors. Data used for the analysis were based on presence and absence of the two species from previous survey collections in the region (mainly Ethiopia, Kenya and Somalia). Annual, wet season and dry season models were constructed. Although all models resulted in more than 85% positive predictive values for both species, the best fit for the distribution of P. martini was the dry season composite (NDVI 0.07-0.38 and LST 22-33 degrees C) with a predictive value of 93.8%, and the best fit for P. orientalis was the wet season composite (NDVI -0.01 to 0.34 and LST 23-34 degrees C) with a predictive value of 96.3%. The two seasonal composites models derived from satellite data were largely similar with best fit models developed based on the CPSZ climate data: average altitude (12-1900m), average annual mean temperature (15-30 degrees C), annual rainfall (274-1212mm), average annual potential evapotranspiration (1264-1938mm) and readily available soil moisture (62-113mm) for P. martini; and average altitude (200-2200m), annual rainfall (180-1050mm), annual mean temperature (16-36 degrees C) and readily available soil moisture (67-108mm) for P. orientalis. Logistic regression analysis indicated LST dry season composite of the satellite data, average altitude, mean annual temperature and readily available soil moisture of the CPSZ data as the best ecological determinants for P. martini while LST annual composite was the only important ecological determinant for P. orientalis. Spearman's rank correlation revealed several factors to be important determinants for the distribution of the two vectors. None of the soil types analysed appeared to be important determinant for the two species in East Africa, unlike in Sudan where P. orientalis is mainly associated with eutric vertisol (black cotton clay soil).