Indications of the Protective Role of Natural Killer Cells in Human Cutaneous Leishmaniasis in an Area of Endemicity

The role of natural versus acquired immunity to Leishmania aethiopica infection in humans is the focus of our studies. We found in previous studies that mononuclear cells from nonexposed healthy Swedish donors responded to Leishmania antigen stimulation by proliferation and gamma interferon production. The main cell type responding was CD3⁻ CD16/56⁺ natural killer (NK) cells. These findings led us to suggest that the potential to produce a rapid, nonacquired NK cell response may be a protective phenotype. In order to test this hypothesis, an area in Ethiopia where Leishmania is endemic was selected, and peripheral blood mononuclear cells were obtained from individuals who had lived in the area most of their lives but had no evidence of past or present leishmaniasis. Their responses were compared with those of confirmed leishmaniasis patients from the same region with active lesions or cured leishmaniasis lesions. Cells from these donors were stimulated in vitro with L. aethiopica antigen. Responses were measured by proliferation, cytokine production, and phenotype analysis by fluorescence-activated cell sorting. The association of NRAMP1 alleles with the studied phenotype and susceptibility to L. aethiopica-induced leishmaniasis was also evaluated. The results show that Leishmania antigens can induce NK cell and CD8⁺-T-cell responses in vitro. This is clearly seen in proliferating cells from the cured (immune) individuals and the apparently protected controls from the area of endemicity. It contrasted with the reactivity of the patients, where some NK proliferation was coupled with enhanced CD4⁺-T-cell proliferation. We conclude from these observations that NK cells and CD8⁺ cells proliferating in response to Leishmania stimulation are involved in protection from and healing of (Ethiopian) cutaneous leishmaniasis; however, such mechanisms appear to be unrelated to the NRAMP1 host resistance gene.     

Ultrasonographic detection of ureteral jets in normal pregnancy

Objective: Our purpose was to determine the impact of normal physiologic urodynamic alterations of pregnancy on the detection of ureteral jets into the bladder with use of transabdominal color Doppler ultrasonography. Study Design: We conducted a prospective cohort study of 125 healthy asymptomatic gravid women without any history of past or current renal disease, all with singleton pregnancies between 13.4 and 37.7 weeks' gestation. Right and left ureteral jets were recorded over a 5-minute period with use of color Doppler transabdominal ultrasonography and a full bladder. Each kidney was graded by the severity of the hydronephrosis. No hydronephrosis was grade 0, mild hydronephrosis was grade 1, and moderate hydronephrosis was grade 2. There were no cases of severe hydronephrosis. Results: There were 56 grade 0 cases on the right versus 93 grade 0 cases on the left (p < 0.0001), 53 versus 30 grade 1 cases (right vs left, p < 0.003) and 16 versus 2 grade 2 cases (right vs left, p < 0.0009). In the subgroup where both kidneys were grade 0 the mean number of right ureteral jets 5 mm was 14.7 versus 15.1 for the left ureteral jets (p = 0.73). In the grade 1 subgroup mean right versus left ureteral jets was 15.4 versus 16.6 (p = 0.65). For the grade 2 subgroup mean right versus left ureteral jets was 15.5 versus 21.0 (p = 0.32). There were 4 of 125 unilateral absent ureteral jets on the right versus 0 of 125 on the left (p = 0.122). Conclusion: Our data demonstrate that ureteral jets can be readily detected during pregnancy independent of the gestational age. In addition, it does not appear that the physiologic urodynamic alterations of pregnancy affect the frequency or symmetry of ureteral jets. Thus identification of ureteral jets can be used in the workup of suspected urolithiasis in pregnant patients. (Am J Obstet Gynecol 1998;178:1194-8.)     

Detection of Leishmania donovani and L. tropica in Ethiopian wild rodents

Human visceral (VL, also known as Kala-azar) and cutaneous (CL) leishmaniasis are important infectious diseases affecting countries in East Africa that remain endemic in several regions of Ethiopia. The transmission and epidemiology of the disease is complicated due to the complex life cycle of the parasites and the involvement of various Leishmania spp., sand fly vectors, and reservoir animals besides human hosts. Particularly in East Africa, the role of animals as reservoirs for human VL remains unclear. Isolation of Leishmania donovani parasites from naturally infected rodents has been reported in several endemic countries; however, the status of rodents as reservoirs in Ethiopia remains unclear. Here, we demonstrated natural Leishmania infections in rodents. Animals were trapped in 41 localities of endemic and non-endemic areas in eight geographical regions of Ethiopia and DNA was isolated from spleens of 586 rodents belonging to 21 genera and 38 species. Leishmania infection was evaluated by real-time PCR of kinetoplast (k)DNA and confirmed by sequencing of the PCR products. Subsequently, parasite species identification was confirmed by PCR and DNA sequencing of the 18S ribosomal RNA internal transcribed spacer one (ITS1) gene. Out of fifty (8.2%) rodent specimens positive for Leishmania kDNA-PCR and sequencing, 10 were subsequently identified by sequencing of the ITS1 showing that five belonged to the L. donovani complex and five to L. tropica. Forty nine kDNA-positive rodents were found in the endemic localities of southern and eastern Ethiopia while only one was identified from northwestern Ethiopia. Moreover, all the ten ITS1-positive rodents were captured in areas where human leishmaniasis cases have been reported and potential sand fly vectors occur. Our findings suggest the eco-epidemiological importance of rodents in these foci of leishmaniasis and indicate that rodents are likely to play a role in the transmission of leishmaniasis in Ethiopia, possibly as reservoir hosts.     

Prevalence of onchocercal skin disease and infection among workers of coffee plantation farms in Teppi,southwestern Ethiopia

In June 1996, a study on the economic impacts of onchocercal skin disease was initiated in southwestern Ethiopia. We made parasitological and clinicoepidemiological investigations among 1619 workers of a coffee plantation firm in Teppi, south-western Ethiopia. Sixty percent of the workers were included in the study. The prevalence of onchocercal skin disease (OSD) was 85.3%. Severe OSD (SOSD) was found in 17.3% of the study subjects. This was 1/5 of all OSD cases. The overall nodule carrier rate was 44.2%, which differed significantly by age classes from a rate of 12.3% to 73.0%. This rate varied by sex, 51.7% in males and 22.6% in females. Microfilarial carrier rate (MFCR) was 77.6%. This rate did not vary neither with severity of disease nor with presence or absence of pruritus or onchodermatitis. Mean microfilarial count was determined to be 38.1 per mg of skin snip or 44.4 per mg of infected skin snips. The geometric mean of microfilarial load per infected skin was 23.8. The community microfilarial load (CMFL) was estimated to be 14.0 per mg skin snip. The study showed that SOSD is prevalent in Teppi and affects a substantial number of the working population. An intervention program is called for.     

Droperidol and diphenhydramine in the management of hyperemesis gravidarum

OBJECTIVE: Hyperemesis gravidarum is a common pregnancy complication requiring hospitalization. Continuous droperidol infusion and bolus intravenous diphenhydramine were instituted as treatment. We compared the number and length of hospitalizations for hyperemesis gravidarum, readmissions for this diagnosis, and pregnancy outcome in patients receiving this treatment protocol with a historic group of patients receiving other forms of parenteral therapy for hyperemesis gravidarum. STUDY DESIGN: All patients hospitalized with a diagnosis of hyperemesis gravidarum between January 1992 and January 1994 were offered the droperidol-diphenhydramine protocol. These patients were compared with patients admitted between January 1990 and January 1992 with a diagnosis of hyperemesis gravidarum but who were not treated with droperidol at any time or with diphenhydramine as primary therapy for the control of severe nausea and vomiting. Data regarding the number and length of hospitalizations and readmissions for hyperemesis gravidarum were compared, as were maternal and perinatal outcomes. RESULTS: Patients treated with the droperidol-diphenhydramine protocol had significantly shorter hospitalizations (3.1 ± 1.9 vs 3.8 ± 2.4 days, p = 0028), fewer days per pregnancy hospitalized for hyperemesis (3.5 ± 2.3 days vs 4.8 ± 4.3 days, p = 0018), and fewer readmissions with this diagnosis (15.0% vs 31.5%, p = 0015). There were no significant differences in maternal or perinatal outcomes. CONCLUSION: Droperidol and diphenhydramine infusion is a beneficial, cost-effective therapy for the treatment of hyperemesis gravidarum. (Am J Obstet Gynecol 1996;174:1801-6.)     

Antimicrobial susceptibility pattern of Helicobacter pylori strains isolated from adult dyspeptic patients in Tikur Anbassa University Hospital, Addis Ababa, Ethiopia

Presently, there is no published information on the antimicrobial susceptibility pattern of H. pylori strains in Ethiopia to guide the choice of drug for therapy. Therefore, it is becoming clinically relevant to test the in vitro susceptibility of H. pylori clinical isolates prior to treating patients. Susceptibility testing was performed on 50 clinical H. pylori isolates obtained from adult dyspeptic patients referred to the gastrointestinal (GI) Clinic of Tikur Anbassa University Hospital. Five antibiotics were evaluated, by using the Episolmeter test (E-test). The antibiogram of 50 H. pylori clinical isolates showed that all strains were sensitive to clarithromycin, erythromycin and tetracycline, while 38/50 (76%) and 3/50 (6%) of the strains were resistant to metronidazole and amoxicillin, respectively. Infection by metronidazole or amoxicillin resistant H. pylori is an important factor leading to treatment failure. Testing of all H. pylori clinical isolates to metronidazole and amoxicillin is recommended. If it is not possible to perform susceptibility tests on each clinical isolate, a program to survey the prevalence of resistance should be implemented in a given area or population. When treatment of H. pylori infection is indicated in dyspeptic patients, the potential availability, simplicity of use, safety and low cost of the antimicrobial agents have to be taken into account.     

Effect of the antenatal administration of celecoxib during the second and third trimesters of pregnancy on prostaglandin, cytokine, and nitric oxide levels in rabbits

OBJECTIVE: The purpose of this study was to examine the effects of celecoxib on prostaglandin, cytokine, and nitric oxide synthesis in the pregnant rabbit. STUDY DESIGN: Pregnant rabbits received celecoxib from 13 to 20 days (celecoxib-A), from 13 to 28 days (celecoxib-B), or vehicle from 13 to 28 days by gavage. Blood and tissue were assayed for prostaglandin, cytokine, and nitric oxide oxidation products. RESULTS: Preterm delivery occurred in 4 of 11 controls, 0 of 9 in celecoxib-A, and 0 of 8 in celecoxib-B. Plasma prostaglandin F(2alpha) was reduced in both treated groups at 20 days and at delivery in celecoxib-B. Plasma thromboxane B(2) was suppressed in celecoxib-B at 20 days and delivery. Cervical prostaglandin E(2) was increased; uterine and cervical plasma thromboxane B(2) declined in celecoxib-B. Celecoxib administration suppressed plasma nitric oxide oxidation products at delivery and cervical nitric oxide oxidation products in celecoxib-B. Uterine and cervical interleukin-1beta and interleukin-6 were decreased, and uterine tumor necrosis factor-alpha increased in celecoxib-B. CONCLUSION: Further studies are required to evaluate the therapeutic benefits of cyclo-oxygenase-2 inhibitors in the setting of preterm parturition.