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The nitrate reductase assay for the rapid detection of isoniazid and rifampicin resistance in Mycobacterium tuberculosis: a systematic review and meta-analysis
No full textObjectives: The reference standard methods for drug susceptibility testing (DST) of M. tuberculosis are very slow to give results, and due to the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis, there is an urgent demand for new, rapid and accurate DST methods, particularly in low-income countries. The nitrate reductase assay (NRA) has been proposed as a rapid method for the detection of resistance to rifampicin and isoniazid, but its accuracy has not been systematically evaluated.
Methods: We performed a systematic review and meta-analysis to evaluate the accuracy of the NRA for the detection of rifampicin- and isoniazid-resistant tuberculosis. We searched Medline PubMed (NCBI), Global Health-CAB, EJS-E (EbscoHost), ISI Web, Web of Science and IFCC and contacted authors if additional information was required. Fifteen studies met our inclusion criteria for rifampicin resistance detection and 13 for isoniazid. Of these, the majority of the studies used culture isolates on solid medium, four used culture isolates on liquid medium and three used sputum samples. We applied the summary receiver operating characteristic (SROC) curve to perform meta-analysis and to summarize diagnostic accuracy.
Results: For rifampicin, the majority of the studies that applied NRA to isolates had a sensitivity and specificity >94% and for isoniazid, >92%. The three studies that applied NRA directly on sputum samples had a sensitivity and specificity that ranged between 88% and 100%. The SROC curve had an area of >0.99 for both drugs.
Conclusions: There is evidence that NRA is highly sensitive and specific for the rapid detection of rifampicin and isoniazid resistance in culture isolates. More evidence is required for the NRA applied directly on sputum samples, but preliminary results appear promising and show a good sensitivity and specificity. Additional studies are required in countries with a high prevalence of MDR-TB and also cost-effectiveness analysis in order to obtain a complete picture on the utility of this method for rapid drug resistance detection in tuberculosis
Higher homologous and lower cross-reactive Gag-specific T-cell responses in human immunodeficiency virus type 2 (HIV-2) than in HIV-1 infection
No full textHuman immunodeficiency virus type 2 (HIV-2) infection results in slower CD4(+) T-cell decline, lower plasma viral load levels, and hence slower progression of the disease than does HIV-1 infection. Although the reasons for this are not clear, it is possible that HIV-2 replication is more effectively controlled by host responses. We used aligned pools of overlapping HIV-1 and HIV-2 Gag peptides in an enhanced gamma interferon enzyme-linked immunospot assay to compare the levels of homologous and cross-reactive Gag-specific T-cell responses between HIV-1- and HIV-2-infected patients. HIV-2-infected patients showed broader and stronger homologous Gag-specific T-cell responses than HIV-1-infected patients. In contrast, the cross-reactive T-cell responses in HIV-2-infected patients were both narrower and weaker than those in HIV-1-infected patients, in line with overall weaker correlations between homologous and heterologous T-cell responses among HIV-2-infected patients than among HIV-1-infected patients. Cross-reactive responses in HIV-2-infected patients tended to correlate directly with HIV-1/HIV-2 Gag sequence similarities; this was not found in HIV-1-infected patients. The CD4(+) T-cell counts of HIV-2-infected patients correlated directly with homologous responses and inversely with cross-reactive responses; this was not found in HIV-1-infected patients. Our data support a model whereby high-level HIV-2-specific T-cell responses control the replication of HIV-2, thus limiting viral diversification and priming of HIV-1 cross-reactive T-cell responses over time. However, we cannot exclude the possibility that HIV-2 replication is controlled by other host factors and that HIV-2-specific T-cell responses are better maintained in the context of slow viral divergence and a less damaged immune system. Understanding the nature of immune control of HIV-2 infection could be crucial for HIV vaccine design
HIV-related incremental yield of bleach sputum concentration and fluorescence technique for the microscopic detection of tuberculosis
No full textBleach sputum concentration and fluorescence microscopy (FM) are reportedly more sensitive than direct Ziehl-Neelsen (ZN) sputum smears for tuberculosis detection, and might be particularly valuable for human immunodeficiency virus (HIV)-positive patients excreting fewer bacilli. This study, implemented in Yaoundé, Cameroon, determined the yield from both direct and bleach-concentrated FM and ZN duplicate smears against culture on Löwenstein-Jensen medium, with HIV testing from the sputa. From 418 HIV-positive and 518 HIV-negative tuberculosis suspects, 185 (44.3%) and 243 (46.9%) cultures, respectively, grew Mycobacterium tuberculosis. Direct ZN was positive for, respectively, 87 (47.0%) and 202 (83.1%) of the culture-positive cases. Proportional incremental yield over direct ZN from ZN and FM bleach smears was 14.9% (P < 10(-3)) and 17.2% (P < 10(-4)) for HIV-positive versus 4.9% (P < 10(-2)) and 2.0% (non-significant) for HIV-negative cases. There was no gain from direct FM. Bleach FM showed 2% excess false positives. The bleach concentration, therefore, increases the yield of ZN and FM, particularly from HIV-positive patients, but with a higher risk for false positives with bleach FM. With excellent baseline direct ZN, the gain remains modest. Field studies under real-life conditions are needed to determine whether it is worth the risks and operational challenges in HIV high-prevalence populations. FM was not more sensitive than ZN in this study, probably because of sub-optimal objective power and background staining. Culture on solid media with sparing laurylsulfate decontamination was clearly superior for HIV-positives, but it remains to be seen if culture also leads to more cases started on treatment routinely
Community perceptions of pre-identification results and methods in six health equity funds areas in Cambodia
No full textMycobacterium tuberculosis strains of Beijing genotype are rarely observed in tuberculosis patients in South America
No full textThe frequency of the Beijing genotype of Mycobacterium tuberculosis as a cause of tuberculosis (TB) in South
America was determined by analyzing genotypes of strains isolated from patients that had been diagnosed with
the disease between 1997 and 2003 in seven countries of the subcontinent. In total, 19 of the 1,202 (1.6%) TB cases
carried Beijing isolates, including 11 of the 185 patients from Peru (5.9%), five of the 512 patients from Argentina
(1.0%), two of the 252 Brazilian cases (0.8%), one of the 166 patients from Paraguay (0.6%) and none of the samples
obtained from Chile (35), Colombia (36) and Ecuador (16). Except for two patients that were East Asian immigrants,
all cases with Beijing strains were native South Americans. No association was found between carrying a strain with
the Beijing genotype and having drug or multi-drug resistant disease. Our data show that presently transmission of
M. tuberculosis strains of the Beijing genotype is not frequent in Latin America. In addition, the lack of association
of drug resistant TB and infection with M. tuberculosis of the Beijing genotype observed presently demands efforts
to define better the contribution of the virulence and lack of response to treatment to the growing spread of Beijing
strains observed in other parts of the world
The role of B-cells and IgM antibodies in parasitemia, anemia, and VSG switching in Trypanosoma brucei-infected mice
No full textAfrican trypanosomes are extracellular parasitic protozoa, predominantly transmitted by the bite of the haematophagic
tsetse fly. The main mechanism considered to mediate parasitemia control in a mammalian host is the continuous
interaction between antibodies and the parasite surface, covered by variant-specific surface glycoproteins. Early
experimental studies have shown that B-cell responses can be strongly protective but are limited by their VSG-specificity.
We have used B-cell (mMT) and IgM-deficient (IgM2/2) mice to investigate the role of B-cells and IgM antibodies in
parasitemia control and the in vivo induction of trypanosomiasis-associated anemia. These infection studies revealed that
that the initial setting of peak levels of parasitemia in Trypanosoma brucei–infected mMT and IgM2/2 mice occurred
independent of the presence of B-cells. However, B-cells helped to periodically reduce circulating parasites levels and were
required for long term survival, while IgM antibodies played only a limited role in this process. Infection-associated anemia,
hypothesized to be mediated by B-cell responses, was induced during infection in mMT mice as well as in IgM2/2 mice, and
as such occurred independently from the infection-induced host antibody response. Antigenic variation, the main immune
evasion mechanism of African trypanosomes, occurred independently from host antibody responses against the parasite’s
ever-changing antigenic glycoprotein coat. Collectively, these results demonstrated that in murine experimental T. brucei
trypanosomiasis, B-cells were crucial for periodic peak parasitemia clearance, whereas parasite-induced IgM antibodies
played only a limited role in the outcome of the infection
Universal access to HIV care: pitfalls and the way forward [editorial]
No full textThe definitive version is available at www3.interscience.wiley.co
Reforma, equidad y eficiencia de los sistemas de salud en Latinoamerica; un analisis para orientar la cooperación española; informe SESPAS 2008
No full textIn the 1990s, international financial multilateral agencies promoted
changes in the way health systems were financed and
organized. Three decades later, equity and efficiency are still
central problems of the health systems in developing countries.
The present article focuses on the health sector reforms
introduced in Latin America in order to draw policy lessons
for Spanish aid. One of those reforms, the introduction of competition
in health insurance management and provision and
the increase of private sector participation – managed competition
–, was widely promoted, despite the lack of empirical
evidence and the opposition from public and scientific sectors.
Years after its implementation, health system financing is still
inequitable and access to health services is far from universal
and adequate due to the barriers imposed by insurers,
among other reasons. Moreover, segmentation in healthcare
provision and inefficiency persist in healthcare systems that
are expensive to manage. The Spanish state, currently undergoing
a process of transformation of its aid model, should
focus its efforts on redressing international agencies’ policies
toward strengthening public health systems in the region and,
at the same time, toward improving the quantity and quality
of aid at country level, favoring the leadership of receiving countries
Quality cesarean delivery in Ouagadougou, Burkina Faso: a comprehensive approach
No full textOBJECTIVE: To assess the effects of a comprehensive intervention (staff training, equipment, internal clinical audits, cost sharing system, patients-providers meetings) in improving cesarean delivery access and quality in an urban district of Burkina Faso. METHODS: We conducted a before-after study in the health district sector 30 in Ouagadougou between 2003 and 2006. We measured cesarean delivery quality (accessibility, diagnosis, procedure, postoperative follow-up) and maternal and neonatal health in 1371 sections. RESULTS: The number of cesarean deliveries performed increased each year, from 42 in 2003 to 630 in 2006. This increase happened without increase in maternal and perinatal post-cesarean mortality (respectively 1.1% and 3.6% in 2006). The cesarean delivery rate for women of the district increased from 1.9% to 3.3% of expected births between 2003 and 2005. CONCLUSION: To improve access to quality cesarean delivery, we have shown that it was necessary to have a systemic approach combining technical, operational, sociocultural, and political factors