Association of ESAT-6/CFP-10-induced IFN-γ, TNF-α and IL-10 with clinical tuberculosis: evidence from cohorts of pulmonary tuberculosis patients, household contacts and community controls in an endemic setting.

Mycobacterium tuberculosis (Mtb) early secreted protein antigen 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) are among candidate vaccines against tuberculosis (TB). Results of experimental animal models show that these antigens are associated with induction of strong T cell immunity [interferon (IFN)-γ production], while others report that these proteins as virulent factors involved in pathogenicity of Mtb infection. However, the role of ESAT-6/CFP-10 during natural Mtb infections in humans has not been established. In this paper we present results of a longitudinal study from an Mtb-infected human population from an endemic setting. Whole blood assay was used to determine levels of IFN-γ, tumour necrosis factor (TNF)-α and interleukin (IL)-10 against rESAT-6/CFP-10 in TB patients, household contacts and community controls. The levels of IFN-γ, TNF-α and IL-10 against rESAT-6/CFP-10 at baseline were significantly higher in patients and community controls than in household contacts. In patients, no significant difference was observed in the level of these cytokines before and after chemotherapy whereas, in contacts, the level of these cytokines increased significantly and progressively over time. The study shows that the levels of IFN-γ, TNF-α and IL-10 against rESAT-6/CFP-10 are depressed during Mtb infection or exposure but are elevated during clinical TB. Our findings from a study of naturally infected human population suggest that IFN-γ, TNF-α and IL-10 against rESAT-6/CFP-10 are markers for clinical TB but not for protective immunity.

The association between multiple intestinal helminth infections and blood group, anaemia and nutritional status in human populations from Dore Bafeno, southern Ethiopia.

In this cross-sectional study, the associations between helminth infections and ABO blood group, anaemia and undernutrition were investigated in 480 febrile outpatients who visited Dore Bafeno Health Centre, southern Ethiopia, in December 2010. Stool specimens were processed using the Kato-Katz method and examined for intestinal helminth infections. Haemoglobin level was measured using a HemoCue machine and blood group was determined using an antisera haemagglutination test. Nutritional status of the study participants was assessed using height and weight measurements. Among the study participants, 50.2% were infected with intestinal helminths. Ascaris lumbricoides (32.7%), Trichuris trichiura (12.7%), Schistosoma mansoni (11.9%) and hookworm (11.0%) were the most frequently diagnosed helminths. The odds of infection and mean eggs per gram of different intestinal helminth species were comparable between the various blood groups. Among individuals who were infected with intestinal helminth(s), the mean haemoglobin level was significantly lower in individuals harbouring three or more helminth species and blood type AB compared to cases with double or single helminth infection and blood type O, respectively. The odds of being underweight was significantly higher in A. lumbricoides and T. trichiura infected individuals of age ≤ 5 and ≥ 20 years, respectively, when compared to individuals of the matching age group without intestinal helminths. In conclusion, infection with multiple intestinal helminths was associated with lower haemoglobin level, which was more severe in individuals with blood type AB. Future studies should focus on mechanisms by which blood group AB exacerbates the helminth-related reduction in mean haemoglobin level.

IgA response to ESAT-6/CFP-10 and Rv2031 antigens varies in patients with culture-confirmed pulmonary tuberculosis, healthy Mycobacterium tuberculosis-infected and non-infected individuals in a tuberculosis endemic setting, Ethiopia.

Little attention has been given to the role of antibodies against Mycobacterium tuberculosis (Mtb) infection. We have compared the levels of IgA and IgG against ESAT-6/CFP-10 and Rv2031c antigens in sera of patients with culture-confirmed pulmonary tuberculosis (PTB), healthy Mtb-infected and non-infected individuals in endemic TB settings. Venous blood samples were collected from 166 study participants; sera were separated and assayed by an enzyme-linked immunosorbent assay (ELISA). QuantiFERON-TB Gold In-Tube (QFTGIT) assay was used for the screening of latent TB infection. The mean optical density (OD) values of IgA against ESAT-6/CFP-10 and Rv2031 were significantly higher in sera of patients with culture-confirmed PTB compared with healthy Mtb-infected and non-infected individuals (P < 0.001). The mean OD values of IgG against ESAT-6/CFP-10 and Rv2031 were also significantly higher in sera of patients with culture-confirmed PTB compared with healthy Mtb-infected and non-infected individuals (P < 0.05). The mean OD values of IgA against both antigens were also higher in sera of healthy Mtb-infected cases compared with non-infected individuals. There were positive correlations (P < 0.05) between the level of IFN-γ induced in QFTGIT assay and the OD values of serum IgA against both antigens in healthy Mtb-infected subjects. This study shows the potential of IgA response against ESAT-6/CFP-10 and Rv2031 antigens in discriminating clinical TB from healthy Mtb-infected and non-infected cases. Nevertheless, further well-designed cohort study is needed to fully realize the full potential of this diagnostic marker.

Intestinal Parasitic Infections among Under-Five Children and Maternal Awareness about the Infections in Shesha Kekele; Wondo Genet; Southern Ethiopia

Background: Few studies have reported the magnitude of intestinal parasitic infections among under-five children in tropical countries. Moreover; there is little information on maternal awareness about intestinal parasitosis. Objective: To determine the prevalence of intestinal parasitosis among under-five children; and assess maternal awareness about it in Shesha Kebkele; Wondo Genet; Southern Ethiopia. Methods: A cross-sectional study involving 288 under-five children was conducted and stool samples were collected and examined for intestinal parasites using Kato-Katz and formol-ether concentration methods. In addition; a total of 130 mothers of under-five children were interviewed regarding their awareness about intestinal parasitic infections. Results: Of the 288 children; 245 (85.1) were found infected with one or more intestinal parasites. The prevalence of Trichuris trichiura; Schistosoma mansoni and Ascaris lumbricoides; hookworm; and Hymenolepis nana infections as determined by Kato-Katz were 74.7; 37.2; 25.7; 5.9; and 4.5; respectively. On the other hand; the prevalence of Strongyloides stercoralis; Giardia lamblia; Entamoeba histolytica/dispar; and Entamoeba coli infections as determined by formol-ether concentration method were 0.69; 13.2; 0.35; and 2.1; respectively. Most mothers were reasonably aware of the mode of transmission of ascariasis; amoebiasis and giardiasis while they had very limited knowledge of bilharzia and hookworm transmission. Almost all of the respondents reported that infections with intestinal parasites could cause retardation of growth and death in children unless treated. Conclusion: Intestinal parasitic infections were prevalent in varying magnitude among under-five children in Wondo Genet area; Southern Ethiopia. Mothers in the study area had a fairly good knowledge of the impact of infections but limited knowledge of the mode of transmission of intestinal parasitic infections. Improvement of sanitation and health education are required besides preventive chemotherapy to control worms (except for schistosomiasis in under-five which need treatment on an individual basis) and other intestinal parasitic infections in the area. (Ethiop. J. Health Dev. 2010;24(3):185-190)

Efficacy of six-dose regimen of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria, three years after its introduction into Ethiopia.

We assessed the clinical and parasitological efficacy of six-dose regimen of artemether-lumefantrine (AL) (Coartem) for treating uncomplicated P. falciparum malaria three years after its introduction into Ethiopia. A total of 102 patients (mean age: 15.7 years; age range: 1-50 years) were enrolled in the study and followed-up for 28 days based on WHO protocol. Treatment with AL resulted in 100% adequate clinical and parasitological response (ACPR). No severe side-effect of the drug was observed. All patients had rapid clinical and parasitological responses. None of the subject was found to be positive for asexual or sexual stage of the parasite after day 3. A significant increase in the mean of haemoglobin level was observed on day 28 posttreatment (11.4 g/dL on day 0 vs 12.3 g/dL on day 28, p < 0.05). Thus, artemisinin-based combination therapies (ACTs) seem to mitigate not only the problem of drug resistance malaria but also the transmission of the disease. Nevertheless, monitoring ACT therapeutic efficacy is crucial in Ethiopia.

Community Awareness about Malaria; its Treatment and Mosquito Vector in rural Highlands of Central Ethiopia

Background: Despite the rapid expansion of malaria into highland areas of Ethiopia and the movement of malaria inexperienced people to endemic areas; there is no enough information about how highland communities perceive malaria. Objective: To assess communities' awareness of malaria and its mosquito vector in highland rural communities of central Ethiopia. Methods: A community-based cross-sectional survey involved 770 heads of household was conducted during September 2005 to February 2006 in nine peasant associations of five purposely selected districts in highland areas where malaria has been recently introduced; or currently free from the disease. Results: The majority of the study participants knew that malaria is a serious disease that can attack all age groups of a population (81.0). A considerable number of individuals; 357 (47.5) responded that they visited malarious area and about 50of these individuals reported that they or their families had got the disease. A large proportion of participants (81.6) mentioned that mosquito transmits malaria through biting (91.6); while 176 (42.6) individuals are aware that mosquitoes bite during night. Participants from Sheno; Muka Turi and Sululita areas were found to better in associating the cause of malaria with mosquito bites than those participants from Ginchi and Holeta areas (p 0.05). In contrast; participants from Ginchi area were found to better in identifying the common signs/symptoms of malaria and recommending modern antimalarial drug for treatment than participants from other localities (p 0.05). Some of the respondents believed that mosquito bites or landing can be prevented using various methods like mosquito net; eating or keeping garlic in pocket; while more than half (67.1) of the participants had no information about preventive methods of mosquito bites. Conclusion: Communities residing in the highland of the present study areas were aware that malaria is a serious disease. However; they had no clear information about its cause; mode of transmission and preventive methods. Hence; emphasis should be given to increase community awareness through implementation of appropriate health education program for prevention and control of the disease from expanding into highland areas of Ethiopia

Community awareness about malaria; its treatment and mosquito vector in rural highlands of central Ethiopia

Background: Despite the rapid expansion of malaria into highland areas of Ethiopia and the movement of malariainexperienced people to endemic areas; there is no enough information about how highland communities perceive malaria. Objective: To assess communities' awareness of malaria and its mosquito vector in highland rural communities of central Ethiopia. Methods: A community-based cross-sectional survey involved 770 heads of household was conducted during September 2005 to February 2006 in nine peasant associations of five purposely selected districts in highland areas where malaria has been recently introduced; or currently free from the disease. Results: The majority of the study participants knew that malaria is a serious disease that can attack all age groups of a population (81.0). A considerable number of individuals; 357 (47.5) responded that they visited malarious area and about 50of these individuals reported that they or their families had got the disease. A large proportion of participants (81.6) mentioned that mosquito transmits malaria through biting (91.6); while 176 (42.6) individuals are aware that mosquitoes bite during night. Participants from Sheno; Muka Turi and Sululita areas were found to better in associating the cause of malaria with mosquito bites than those participants from Ginchi and Holeta areas (p 0.05). In contrast; participants from Ginchi area were found to better in identifying the common signs/symptoms of malaria and recommending modern antimalarial drug for treatment than participants from other localities (p 0.05). Some of the respondents believed that mosquito bites or landing can be prevented using various methods like mosquito net; eating or keeping garlic in pocket; while more than half (67.1) of the participants had no information about preventive methods of mosquito bites. Conclusion: Communities residing in the highland of the present study areas were aware that malaria is a serious disease. However; they had no clear information about its cause; mode of transmission and preventive methods. Hence; emphasis should be given to increase community awareness through implementation of appropriate health education program for prevention and control of the disease from expanding into highland areas of Ethiopia

Field-based evaluation of a reagent strip test for diagnosis of schistosomiasis mansoni by detecting circulating cathodic antigen (CCA) in urine in low endemic area in Ethiopia.

The sensitivity, specificity, positive and negative predictive values of a reagent strip test for the diagnosis of schistosomiasis mansoni by detecting circulating cathodic antigen (CCA) in urine were evaluated using 184 stool and urine samples collected from schoolchildren living in relatively low endemic area of schistosomiasis mansoni in Ethiopia. A combined result of stool samples processed by Kato and formol-ether concentration methods was used as gold standard. The results showed that detection of CCA in urine using reagent strip test was slightly higher than the combined results of the stool techniques (65.2 % vs 42.4 %, p > 0.05) in suggesting the prevalence of the disease. The sensitivity, specificity, positive and negative predictive values of the reagent strip test were 76.9 %, 43.4 %, 50 % and 71.9 %, respectively. The result of egg counts using Kato method suggested that detection of urine CCA could be used to indicate the intensity of infection. Nevertheless, like that of stool examination, the reagent strip test was found to be less sensitive in case of light to moderate infections. About 23.1 % of the study children who were excreting the eggs of the parasite were found negative by the reagent strip test. The relative insensitivity of a reagent strip test in low intensity of infection necessitates for the development of more sensitive assay that can truly discriminate schistosome-infected from non-infected individuals.

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.

Comparative efficacy of albendazole and three brands of mebendazole in the treatment of ascariasis and trichuriasis.

OBJECTIVE: To evaluate the comparative efficacy of 400 mg albendazole (Smith Kline Beecham) as a single dose and three brands of mebendazole (Janssen, Unibios and East African Pharmaceuticals) at doses of 100 mg twice a day for three consecutive days in the treatment of single or mixed infections with Ascaris lumbricoides and or Trichuris trichiura in four treatment groups of school children. DESIGN: Randomized trial. SETTING: Wondo-Genet, southern Ethiopia. SUBJECTS: School children, aged six to nineteen years. RESULTS: The percentage cure rate and egg reduction rate obtained with albendazole and mebendazole from the three brands were not significantly different in the treatment of ascariasis. However, significant differences were found among the percentage cure rates and egg reduction rates of the four treatment groups in the treatment of trichuriasis. Comparatively, high cure rate (89.8%) and egg reduction rate (99.1%) were observed in vermox (Janssen) treated group followed by Unibios (India) treated group (53.3% and 96.53% cure and egg reduction rates, respectively), whereas low cure rate (17.1%) and egg reduction rate (69.8%) were seen in the albendazole treated group. CONCLUSION: The results of this study suggest that in areas of single or mixed infections with Trichuris trichiura and/or Ascaris lumbricoides are common public health problems and where laboratory facilities are not available to make parasite identification, mebendazole (particularly vermox, a product of Janssen laboratory) would be the drug of choice to treat trichuriasis and ascariasis. However, either mebendazole from the different brands or albendazole is effective in the treatment of ascariasis in areas where trichuriasis is not prevalent.