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New anti-tuberculosis drugs: strategies, sources and new molecules
No full textTuberculosis is still a major health problem worldwide. Although treatment regimens currently available can cure almost all tuberculosis drug susceptible cases, problems such as the length of treatment, the need for multidrug therapy, the emergence of drug resistance, HIV co-infection and persistent Mycobacterium tuberculosis bacilli, stress the need for new anti-tuberculosis drugs. Strategies to search for new anti-tuberculosis drugs involve: screening libraries of small molecules and natural products or the previous identification of targets crucial to the microorganism and the subsequent design of new molecules. Development of new drugs from known compounds having already shown safety and efficacy is an attractive strategy from the economical, pharmaceutical and clinical point of view. Several derivatives of known molecules and new compounds with different targets have been studied with promising preliminary results. Anti-tuberculosis compounds from natural sources have an enormous potential for the development of new drugs, which have shown not only antimicrobial activity per se but also inhibition of the mechanism of resistance (e.g. efflux pumps) or modulation of the immune response (e.g. macrophage stimulation). If these new drugs are going to have an impact in the treatment of the disease they should ideally be active not only against multiplying microorganisms but also against persistent or dormant bacilli. Due to the complexity of the pathology of M. tuberculosis it is unlikely that a single new drug will be enough. This review will discuss strategies for evaluating drug candidates, new targets, new compounds obtained from synthesis and natural sources, and clinical trials that are currently in progress
Time delays in diagnosis of pulmonary tuberculosis: a systematic review of literature
No full textBACKGROUND: Delay in diagnosis of pulmonary tuberculosis results in increasing severity, mortality and transmission. Various investigators have reported about delays in diagnosis of tuberculosis. We aimed at summarizing the data on these delays in diagnosis of tuberculosis. METHODS: A systematic review of literature was carried out. Literature search was done in Medline and EMBASE from 1990 to 2008. We used the following search terms: delay, tuberculosis, diagnosis, and help-seeking/health-seeking behavior without language restrictions. In addition, indices of four major tuberculosis journals were hand-searched. Subject experts in tuberculosis and authors of primary studies were contacted. Reference lists, review articles and text book chapters were also searched. All the studies were assessed for methodological quality. Only studies carried out on smear/culture-positive tuberculosis patients and reporting about total, patient and health-care system delays were included. RESULTS: A total of 419 potential studies were identified by the search. Fifty two studies qualified for the review. The reported ranges of average (median or mean) total delay, patient delay, health system delay were 25-185 days, 4.9-162 days and 2-87 days respectively for both low and high income countries. Average patient delay was similar to health system delay (28.7 versus 25 days). Both patient delay and health system delay in low income countries (31.7 days and 28.5 days) were similar to those reported in high income countries (25.8 days and 21.5 days). CONCLUSION: The results of this review suggest that there is a need for revising case-finding strategies. The reported high treatment success rate of directly observed treatment may be supplemented by measures to shorten the delay in diagnosis. This may result in reduction of infectious cases and better tuberculosis control
Incidence des infections à Neisseria gonorrhoeae en Belgique: tendances 2000-2006
No full textIn Belgium, three registration systems collect epidemiological information on N. gonorrhoeae infections. The descriptive analysis of the data presented in this article allows describing the epidemiology of N. gonorrhoeae infections in Belgium in terms of trends in time, describing the characteristics of the patients, and providing information on resistance to antibiotics. The results on the incidence of N. gonorrhoeae infections show an important increase since the year 2000, and this increase is even more pronounced between 2005 and 2006. The majority of the patients reside in big cities, mainly in the district of Antwerp and in the Brussels-Capital region. Among the N. gonorrhoeae specimens that were sent to the reference laboratory, the proportion of specimens resistant to ciprofloxacine increases each year ; this proportion reaches 61,4 % in 2006. The increase in the incidence of N. gonorrhoeae infections and in antimicrobial resistance is also observed in other European countries. The increase in incidence may be partly related to the important increase of resistance to ciprofloxacine. It is very important to continue the surveillance of antimicrobial resistance, to adapt treatment in function of the recent evolutions and to inform physicians at a regular basis. The results show that homo- and bisexual men are most at risk for N. gonorrhoeae infections. The prevention campaigns for sexually transmitted infections and screening policy have to be reinforced, particularly among homo- and bisexual men
Journeys to tuberculosis treatment: a qualitative study of patients, families and communities in Jogjakarta, Indonesia
No full textBACKGROUND: Many tuberculosis (TB) patients in Indonesia are diagnosed late. We seek to document patient journeys toward TB diagnosis and treatment and factors that influence health care seeking behavior. METHODS: TB patients in Jogjakarta municipality (urban) and Kulon Progo district (rural) were recruited from health care facilities participating in the DOTS strategy and health care facilities not participating in the DOTS strategy, using purposive sampling methods. Data were collected through in-depth interviews with TB patients and members of their family and through Focus Group Discussions (FGD) with community members. RESULTS: In total, 67 TB patients and 22 family members were interviewed and 6 FGDs were performed. According to their care seeking behavior patients were categorized into National TB program's (NTP) dream cases (18%), 'slow-but-sure patients' (34%), 'shopaholics' (45%), and the NTP's nightmare case (3%). Care seeking behavior patterns did not seem to be influenced by gender, place of residence and educational level. Factors that influenced care seeking behavior include income and advice from household members or friends. Family members based their recommendation on previous experience and affordability. FGD results suggest that the majority of people in the urban area preferred the hospital or chest clinic for diagnosis and treatment of TB whereas in the rural area private practitioners were preferred. Knowledge about TB treatment being free of charge was better in the urban area. Many community members from the rural area doubted whether TB treatment would be available free of charge. CONCLUSION: Most TB patients took over a month to reach a DOTS facility after symptoms appeared and had consulted a number of providers. Their income and advice from household members and friends were factors that influenced their care seeking behavior most
Evaluation of the SD FK70 malaria Ag Plasmodium vivax rapid diagnostic test in a non-endemic setting
No full textBACKGROUND: For clinical and epidemiological reasons, it is interesting to diagnose non-falciparum malaria to the species level. This retrospective study assessed the performance of the SD BIOLINE Malaria Antigen Pv test (FK70), a two-band immunochromatographic test detecting Plasmodium vivax-specific lactate dehydrogenase, on samples of international travellers in a non-endemic setting. METHODS: Stored blood samples from international travellers suspected of malaria were used, with microscopy corrected by PCR as the reference method. Samples infected by Plasmodium vivax (n = 100), Plasmodium falciparum (n = 75), Plasmodium ovale (n = 75) and Plasmodium malariae (n = 25) were included, as well as 100 malaria-negative samples. End points were sensitivity, specificity, inter-reader reliability and reproducibility. RESULTS: The overall sensitivity of the FK70 for the diagnosis of P. vivax was 88.0% (95% confidence interval (CI): 83.6% - 90.3%). For parasite densities > 500/microl, a sensitivity of 97.2% (CI: 92.6% - 99.1%) was obtained. Specificity was 98.5%, with 4 out of 75 P. falciparum samples testing positive. None of the P. ovale samples tested positive. Nearly two-thirds (57/88, 64.7%) of positive P. vivax samples showed faint or weak line intensities, with stronger line intensities at higher parasite densities. The test showed excellent reproducibility and reliability for test results and line intensities (kappa values exceeding 0.98 and 0.87 respectively). CONCLUSION: The FK70 test performed well in diagnosing P. vivax infections in a non-endemic reference setting. It can be of added value to microscopy in species differentiation of malaria infections, especially at parasite densities > 500/microl
Chikungunya infection confirmed in a Belgian traveller returning from Phuket (Thailand)
No full textChikungunya infection has been increasingly reported in international travellers following its epidemic re-emergence in the
Indian Ocean islands in 2006 and its spread to southern Asia thereafter. We describe the first case of chikungunya in a Belgian
traveller returning from Phuket, Thailand and discuss the potential implications of chikungunya cases imported to European countries for patient management and public health
Towards a new reference test for surra in camels
No full textCurrent serological diagnosis of Trypanosoma evansi infection in camels is based on the native variable antigen type RoTat 1.2. The goal of this study was to develop a novel serological diagnostic test based on a nonvariable protein and freed from the use of rats or mice for its production. An enzyme-linked immunosorbent assay using a recombinant extracellular domain of invariant surface glycoprotein 75 (ELISA/rISG75) was developed and tested on a collection of 184 camel sera. The results were compared to those obtained from three established antibody detection tests based on variable surface glycoprotein RoTat 1.2: an ELISA for T. evansi (ELISA/T. evansi), a card agglutination test for trypanosomiasis (CATT/T. evansi), and an immune trypanolysis (TL) assay. The ELISA/rISG75 and the ELISA/T. evansi showed a sensitivity of 94.6% (95% confidence interval [CI], 87.8 to 98.2%, at 19% positivity cutoff value) and 98.9% (95% CI, 94.1 to 99.8, at 12% positivity cutoff value), respectively. The ELISA/rISG75 had 100% specificity (CI, 95.9 to 100%), while the ELISA/T. evansi showed 98.9% specificity (CI, 95.9 to 100%). The ELISA/rISG75 demonstrated an almost perfect agreement with the TL assay, the CATT/T. evansi, and the ELISA/T. evansi, with kappa scores of at least 0.94. The ELISA/rISG75, having a performance comparable to that of the gold standard (the TL assay) and being independent of antigenic variation, may become a new reference test for surra in camels. It opens avenues for the diagnosis of T. evansi infections in other hosts as well as for the development of a pan-Trypanozoon test for detection of Trypanosoma brucei brucei, T. b. gambiense, T. b. rhodesiense, T. evansi, and T. equiperdum
Two vs. three sputum samples for microscopic detection of tuberculosis in a high HIV prevalence population
No full textSETTING: A busy urban hospital in Cameroon. OBJECTIVES: To compare the yield in bacteriologically proven tuberculosis (TB) cases examining two morning vs. three spot-morning-spot sputum specimens (MM vs. SMS) by direct microscopy for acid-fast bacilli (AFB). DESIGN: Repeated temporal cross-over between MM and SMS sampling for successive TB suspects, using culture as gold standard. RESULTS: A total of 799 suspects were screened using the MM strategy, identifying 223 smear-positives, and 808 suspects with the SMS strategy, yielding 236 smear-positives. Of the MM, 256 were culture-positive, of whom 195 (76%) were smear-positive. For SMS, these figures were respectively 281 and 206 (73%), a non-significant difference. The MM and SMS strategies also detected respectively 28 and 30 smear-positive cases not confirmed by culture. No cases were lost to treatment with either strategy. CONCLUSIONS: In this population with a high prevalence of human immunodeficiency virus (HIV) with late case presentation, smear microscopy of two morning specimens detected at least as many positive cases as the classical strategy, and no cases were lost before treatment. Two specimens for initial TB suspect screening can thus be recommended, also without excessive workload. Comparative studies in populations presenting with paucibacillary sputum are needed to determine the equivalent quality and yield of an alternative strategy with two spot specimens at consultation
LC-MS analysis of 13,28-epoxy-oleanane saponins in Maesa spp. extracts with antileishmanial activity
No full textINTRODUCTION: Saponins are natural products that are well known for a wide range of biological activities. For saponins of Maesa balansae, selective antileishmanial activity has been described. OBJECTIVE: In view of their pharmacological interest, several Maesa species from the National Botanical Garden of Meise (Belgium) and wild-grown plants from Vietnam were screened for their antileishmanial potential and saponin content. METHODOLOGY: Different parts of the plants (mainly leaves and twigs) were collected, dried and extracted. Plant extracts were evaluated by liquid chromatography/mass spectrometry (LC-MS) using electrospray ionisation in the negative ion mode and their saponin content was compared with those of Maesa balansae (maesabalides) and Maesa lanceolata (maesasaponins). RESULTS: Several Maesa species (M. ambigua, M. argentea, M. brevipaniculata, M. japonica and M. perlarius) showed potent antileishmanial activity (<0.1 microg/mL) and indeed contained known maesasaponins and maesabalides. However the leaves of M. argentea also revealed two new compounds. Two saponins with [M - H]- ions at m/z 1465 and 1477 were characterised. Their mass spectrometric fragmentation pattern revealed a structure that was the same or closely related to maesasaponin V.3 and VI.2, respectively, but had a glycan part with one additional hexose residue. CONCLUSION: Several known as well as new saponins from Maesa species active against leishmaniasis were characterised using LC-MS
Assessment of the prozone effect in malaria rapid diagnostic tests
No full textBACKGROUND: The prozone effect (or high doses-hook phenomenon) consists of false-negative or false-low results in immunological tests, due to an excess of either antigens or antibodies. Although frequently cited as a cause of false-negative results in malaria rapid diagnostic tests (RDTs), especially at high parasite densities of Plasmodium falciparum, it has been poorly documented. In this study, a panel of malaria RDTs was challenged with clinical samples with P. falciparum hyperparasitaemia (> 5% infected red blood cells). METHODS: Twenty-two RDT brands were tested with seven samples, both undiluted and upon 10 x, 50 x and 100 x dilutions in NaCl 0.9%. The P. falciparum targets included histidine-rich protein-2 (HRP-2, n = 17) and P. falciparum-specific parasite lactate dehydrogenase (Pf-pLDH, n = 5). Test lines intensities were recorded in the following categories: negative, faint, weak, medium or strong. The prozone effect was defined as an increase in test line intensity of at least one category after dilution, if observed upon duplicate testing and by two readers. RESULTS: Sixteen of the 17 HRP-2 based RDTs were affected by prozone: the prozone effect was observed in at least one RDT sample/brand combination for 16/17 HRP-2 based RDTs in 6/7 samples, but not for any of the Pf-pLDH tests. The HRP-2 line intensities of the undiluted sample/brand combinations with prozone effect (n = 51) included a single negative (1.9%) and 29 faint and weak readings (56.9%). The other target lens (P. vivax-pLDH, pan-specific pLDH and aldolase) did not show a prozone effect. CONCLUSION: This study confirms the prozone effect as a cause of false-negative HRP-2 RDTs in samples with hyperparasitaemia