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Identification of stage biomarkers for human African trypanosomiasis
No full textHuman African trypanosomiasis (HAT), caused by infection with sub-species of Trypanosoma brucei (T. b.), manifests as a hemolymphatic stage followed by an encephalitic stage. The distinction of the two stages needs improvement as drugs used for the late stage are highly toxic. Transcripts encoding 16 secreted proteins differentially expressed in the brains of mice at late stage T. b. brucei infection when the early stage drug suramin is no longer effective and different to immunoglobulins, chemokines, and cytokines, were selected by microarray analysis. Lipocalin 2 and secretory leukocyte peptidase inhibitor (SLPI) mRNA showed the highest differential expression in mice. These transcripts were also upregulated in brains from infected rats. Lipocalin 2 was increased in cerebrospinal fluid (CSF) from rats during late stage T. b. brucei infection. Protein levels of lipocalin 2, SLPI, and the chemokine CXCL10 were found increased in CSF from Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense late stage HAT compared to early stag
Antibody responses to the host-protective Taenia solium oncosphere protein TSOL18 in pigs are directed against conformational epitopes
No full textTSOL18 is a recombinant protein that has been shown in repeated experimental trials to be capable of protecting pigs against challenge infection with the cestode parasite Taenia solium. Antibodies raised by the vaccine are capable of killing the parasite in an in vitro culture and it is believed that antibody and complement-mediated killing of invading parasites is the major protective immune mechanism induced by vaccination with TSOL18. Investigations were undertaken to characterize whether the principal antibody specificities raised by TSOL18 in pigs were against linear or conformational determinants. TSOL18 was expressed in two truncated forms representing either the amino terminal portion or the carboxy terminal portion, with the two truncations overlapping in sequence by 25 amino acids. The original protein (designated TSOL18N(-)) and the two truncations (TSOL18N(-)-1 and TSOL18N(-)-2) were used in inhibition ELISA. TSOL18N(-) was shown to be capable of completely inhibiting the binding of pig anti-TSOL18N(-) antibodies to TSOL18N(-) in ELISA. However, neither TSOL18N(-)-1 nor TSOL18N(-)-2, either alone or when combined together, was capable of inhibiting any detectable amount of reactivity of pig anti-TSOL18N(-) antibodies with TSOL18N(-). It is concluded that the dominant antibody specificities, and probably the host-protective specificities, of TSOL18 are conformational epitope
Evaluation of a rapid diagnostic test (CareStartTM Malaria HRP-2/pLDH (Pf/pan) Combo Test) for the diagnosis of malaria in a reference setting
No full textBACKGROUND: Malaria Rapid Diagnostic Tests (RDTs) are widely used for diagnosing malaria. The present retrospective study evaluated the CareStartTM Malaria HRP-2/pLDH (Pf/pan) Combo Test targeting the Plasmodium falciparum specific antigen histidine-rich protein (HRP-2) and the pan-Plasmodium antigen lactate dehydrogenase (pLDH) in a reference setting. METHODS: The CareStartTM Malaria HRP-2/pLDH (Pf/pan) Combo Test was evaluated on a collection of samples obtained in returned international travellers using microscopy corrected by PCR as the reference method. Included were P. falciparum (n=320), Plasmodium vivax (n=76), Plasmodium ovale (n=76), Plasmodium malariae (n=23) and Plasmodium negative samples (n=95). RESULTS: Overall sensitivity for the detection of P. falciparum was 88.8%, increasing to 94.3% and 99.3% at parasite densities above 100 and 1,000/ul respectively. For P. vivax, P. ovale and P. malariae, overall sensitivities were 77.6%, 18.4% and 30.4% respectively. For P. vivax sensitivity reached 90.2% for parasite densities above 500/ul. Incorrect species identification occurred in 11/495 samples (2.2%), including 8/320 (2.5%) P. falciparum samples which generated only the pan-pLDH line. For P. falciparum samples, 205/284 (72.2%) HRP-2 test lines had strong or medium line intensities, while for all species the pan-pLDH lines were less intense, especially in the case of P. ovale. Agreement between observers was excellent (kappa values > 0.81 for positive and negative readings) and test results were reproducible. The test was easy to perform with good clearing of the background. CONCLUSION: The CareStartTM Malaria HRP-2/pLDH (Pf/pan) Combo Test performed well for the detection of P. falciparum and P. vivax, but sensitivities for P. ovale and P. malariae were poo
Phenotypic and genotypic characterisation of Brucella strains isolated from cattle in the Gambia
No full textThirty-five serum samples and six hygroma fluid samples were collected from sexually mature cattle in one herd with clinical signs of brucellosis (abortion and hygromas) in the Western Region of the Gambia in order to isolate and characterise Brucella species. Information on the sex, age, number of calvings, number of abortions, presence of hygromas, and presence of orchitis was also collected for each animal sampled. Twenty-six (74 per cent) of the serum samples were positive in the rose bengal test and 29 (83 per cent) were positive by indirect ELISA. Three isolates of Brucella, biotyped as Brucella abortus biovar 3, were cultured from six hygroma fluid samples. The multiple locus variable number tandem repeat analysis assay clustered the isolates as B abortus with the same profile for the three isolates, suggesting a common origin of contaminatio
Phase II evaluation of sensitivity and specificity of PCR and NASBA followed by oligochromatography for diagnosis of human African trypanosomiasis in clinical samples from D.R. Congo and Uganda
No full textBACKGROUND: The polymerase chain reaction (PCR) and nucleic acid sequence-based amplification (NASBA) have been recently modified by coupling to oligochromatography (OC) for easy and fast visualisation of products. In this study we evaluate the sensitivity and specificity of the PCR-OC and NASBA-OC for diagnosis of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense human African trypanosomiasis (HAT). METHODOLOGY AND RESULTS: Both tests were evaluated in a case-control design on 143 HAT patients and 187 endemic controls from the Democratic Republic of Congo (DRC) and Uganda. The overall sensitivity of PCR-OC was 81.8% and the specificity was 96.8%. The PCR-OC showed a sensitivity and specificity of 82.4% and 99.2% on the specimens from DRC and 81.3% and 92.3% on those from Uganda. NASBA-OC yielded an overall sensitivity of 90.2%, and a specificity of 98.9%. The sensitivity and specificity of NASBA-OC on the specimens from DRC was 97.1% and 99.2%, respectively. On the specimens from Uganda we observed a sensitivity of 84.0% and a specificity of 98.5%. ONCLUSIONS/SIGNIFICANCE: The tests showed good sensitivity and specificity for the T. b. gambiense HAT in DRC but rather a low sensitivity for T. b. rhodesiense HAT in Ugand
National anti-tuberculosis drug resistance study in Tanzania
No full textOBJECTIVE: To assess the prevalence of anti-tuberculosis drug resistance in a national representative sample of tuberculosis (TB) patients in Tanzania according to recommended methodology. DESIGN: Cluster survey, with 40 clusters sampled proportional to size, of notified TB patients from all diagnostic centres in the country. RESULTS: The survey enrolled 1019 new and 148 retreatment patients. The adjusted prevalence of Mycobacterium tuberculosis strains resistant to any of the four first-line drugs in new patients was 8.3%, while the prevalence of multidrug-resistant TB (MDR-TB) was 1.1%. In retreatment patients, the crude prevalence for any resistance and for MDR-TB was respectively 20.6% and 3.9%. The prevalence of drug resistance did not differ in relapse patients compared to failure patients. These estimates are among the lowest in those African countries with an estimated level of drug resistance in the last 5 years. CONCLUSION: The low levels of drug resistance in Tanzania are likely due to a well performing TB control programme and the absence of noticeable involvement of the private sector in TB treatmen
Efficacy of Cymelarsan((R)) and Diminasan((R)) against Trypanosoma equiperdum infections in mice and horses
No full textTrypanocidal sensitivity studies were conducted to assess the efficacy of Diminazene diaceturate (Diminasan((R))) and Bis (aminoethylthio) 4-melaminophenylarsine dihydrochloride (Cymelarsan((R))) against Trypanosoma equiperdum (isolated from two mares with chronic cases of dourine) 713/943 and 834/940 Dodola strains in experimentally infected mice and horses. Diminasan((R)) at doses from 3.5mg/kg to 28mg/kg and Cymelarsan((R)) at doses of 0.25mg/kg and 0.5mg/kg body weight failed to cure any of the mice, indicating a clear dose dependent relationship in the mean time of relapse observed in mice. Indeed, mice treated with lower doses relapsed after a shorter time than mice treated with higher doses. However, mice treated with Cymelarsan((R)) at doses of 1.0mg/kg and 2.0mg/kg body weight were cured and no parasitemia was observed for 60 days. The efficacy of Cymelarsan((R)) was also tested in horses. Two groups of horses containing two animals each were infected with T. equiperdum 834/940 Dodola strain and treated with Cymelarsan((R)) at a dose rate of 0.25mg/kg and 0.5mg/kg, respectively. Cymelarsan((R)) at 0.25mg/kg and 0.5mg/kg body weight cleared parasitemia within 24h post treatment and none of the animals were found to show relapse throughout the 320 days of observation. The sensitivity of the particular trypanosome strain to Cymelarsan((R)) was also supported by the relative improvement in the mean PCV levels of horses following treatment. A statistically significant difference (p<0.01) in the mean PCV levels of horses treated with Cymelarsan((R)) was observed between day 20 at peak parasitemia and days 40 as well as 60 of observation. The mean PCV levels of horses in the control group progressively decreased within the first 60 days of post infection. Two of the horses in the control group developed chronic form of dourine manifested by genital as well as nervous signs with progressive loss of body condition within 320 days post infection. The efficacy of Cymelarsan((R)) against the chronic form of dourine was confirmed after treatment of one of the control horses with Cymelarsan((R)) at a dose rate of 0.25mg/kg body weight at day 282 post infection. It was noted that the treated horse improved overall body condition and clinical signs such as incoordination of hind legs, weakness and ventral oedema disappeared within 10 days of treatment. Thus, Cymelarsan((R)) was found to be quite effective in curing horses in acute as well as chronic form of dourine. The results obtained from the present study will be important for designing effective control measures against dourin
Reducing pediatric HIV infection: estimating mother to child transmission rates in a program setting in Zambia
No full textBACKGROUND:: Vertical transmission of HIV remains the main source of pediatric HIV infection in Africa with transmission rates as high as 25%-45% without intervention. Even though effective interventions to reduce vertical transmission of HIV are now available and remarkable progress has been made in scaling up prevention of mother to child transmission (PMTCT) services, the effectiveness of PMTCT interventions is unknown in Zambia. In this study, we estimate HIV vertical transmission rates at different age bands among perinatally exposed children. METHODS:: The study analyzed program data of DNA polymerase chain reaction results and selected client information on dried blood spot samples from perinatally exposed children aged 0-12 months sent to the polymerase chain reaction laboratory from 5 provinces between September 2007 and January 2009. RESULTS:: Samples of 8237 babies between 0 and 12 months were analyzed, with 84% of the mothers having ever breastfed their children. The observed transmission rate was 6.5% (5.1%, 7.8%) among infants aged 0-6 weeks when both mother and infant received interventions compared with 20.9% (12.3%, 29.5%) where no intervention was given to either mother or baby. Observed HIV transmission with single-dose nevirapine (sdNVP) was 8.5% (5.9%, 11.0%) among infants aged 0-6 weeks, whereas zidovudine with sdNVP (zidovudine + NVP) and highly active antiretroviral therapy were associated with observed transmission rates of 6.8% (4.5%, 9.1%) and 5.0% (3.0%, 7.0%), respectively; whereas these estimates were not significantly different from one another, they were all significantly lower than no intervention for which the estimated rate was 20.9%. Regardless of the intervention, the observed transmission rates were higher among infants aged 6-12 months. CONCLUSIONS:: PMTCT interventions, including sdNVP, are working in program settings. However, postnatal transmission especially after 6 months through suboptimal feeding practises remains an important challenge to further reduce pediatric HI