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Randomized controlled trial of 2 prenatal iron supplements: is there a dose-response relation with maternal hemoglobin?
No full textBACKGROUND: The most appropriate dose of iron to prevent maternal anemia is still unclear. OBJECTIVE: We assessed the dose-response relation between maternal hemoglobin and 2 prenatal iron supplements. DESIGN: An intention-to-treat, double-blind, randomized controlled trial compared 30 mg Fe + folic acid and 13 other micronutrients (UNIMMAP; UNICEF/WHO/UNU multiple micronutrient supplement for pregnant and lactating women) with 60 mg Fe + folic acid (IFA) only in rural Burkina Faso. Home visitors directly observed tablet intake. Mixed-effects models were used for the data analysis. RESULTS: At inclusion, 43.2% of the 1268 participants were anemic. On average, the hemoglobin concentration decreased over gestation by 0.019 g/dL (95% CI: 0.012, 0.025 g/dL) per week in the IFA and UNIMMAP groups. An increment in hemoglobin concentration per micronutrient tablet [beta (+/-SE) = 0.006 +/- 0.001 g/dL; P < 0001] was observed only in women who were anemic at inclusion, whereas a decrease was observed in the other mothers (-0.003 +/- 0.001 g/dL; P = 0.002, P for interaction < 0.0001); the finding was similar in both the IFA and UNIMMAP groups. Women with baseline anemia achieved the same hemoglobin concentration (mean +/- SD: 11.1 +/- 0.64 g/dL) as their counterparts who received +/-180 tablets of either UNIMMAP or IFA. Despite this, micronutrient intake did not significantly prevent anemia (51.0% in the third trimester). It was, however, a risk factor for hemoconcentration (odds ratio per tertile of tablet intake: 2.10; 95% CI: 1.12, 3.94), independently of supplement type or initial hemoglobin concentration. CONCLUSIONS: UNIMMAP triggered the same hemoglobin dose response with half the amount of iron as provided by IFA treatment. The benefit of iron supplements in nonanemic women is unclear. Despite micronutrient supplementation, anemia remained highly prevalent during gestation, partly because of physiologic hemodilution. This trial was registered at clinicaltrials.gov as NCT00642408
Interferon-Gamma Release Assay (Modified QuantiFERON) as a potential marker of infection for Leishmania donovani, a proof of concept study
No full textBACKGROUND: In areas endemic for visceral leishmaniasis (VL), a large number of infected individuals mount a protective cellular immune response and remain asymptomatic carriers. We propose an interferon-gamma release assay (IFN-gammaRA) as a novel marker for latent L. donovani infection. METHODS AND FINDINGS: We modified a commercial kit (QuantiFERON) evaluating five different leishmania-specific antigens; H2B, H2B-PSA2, H2B-Lepp12, crude soluble antigen (CSA) and soluble leishmania antigen (SLA) from L. donovani with the aim to detect the cell-mediated immune response in VL. We evaluated the assay on venous blood samples of active VL patients (n = 13), cured VL patients (n = 15), non-endemic healthy controls (n = 11) and healthy endemic controls (n = 19). The assay based on SLA had a sensitivity of 80% (95% CI = 54.81-92.95) and specificity of 100% (95% CI = 74.12-100). CONCLUSION: Our findings suggest that a whole-blood SLA-based QuantiFERON assay can be used to measure the cell-mediated immune response in L. donovani infection. The positive IFN-gamma response to stimulation with leishmania antigen in patients with active VL was contradictory to the conventional finding of a non-proliferative antigen-specific response of peripheral blood mononuclear cells and needs further research
Operational assessment of access to ART in rural Africa: the example of Kisantu in Democratic Republic of the Congo
No full textDespite the availability of large funds and considerable efforts to improve access to antiretroviral therapy (ART), coverage of treatment with ART remains low in Democratic Republic of the Congo (DRC). We identified the bottlenecks for adults' access to ART in a semi-rural health zone in DRC, compared ART coverage in the urban and rural area and described the outcomes and yield of different HIV testing settings. An operational model was used to examine bottlenecks in the flow of patients. The study period covered the start of the HIV care programme in April 2006, until December 2008. An estimated 505 People Living With HIV/AIDS (PLWHA), of whom 201 were in need of ART, lived in the health zone. The proportion of PLWHA in need of ART who were actually receiving ART was estimated at 53%. About 6451 adults were tested for HIV, 266 of them were HIV-positive and 163 accessed the HIV care programme. About 106 of the 126-159 eligible patients initiated ART. The main bottleneck was situated at HIV detection. Access to the HIV care programme for the patients testing HIV-positive was identified as the second biggest bottleneck. About 41% of the PLWHA identified in urban areas accessed the HIV care programme, versus 11% of the rural PLWHA, showing a serious inequity. The tuberculosis (TB) programme detected 75% of the total estimated 92 co-infected patients of the health zone. Only 13% of women testing positive in the Prevention of Mother-To-Child Transmission programme accessed the HIV care programme, showing that this bottleneck is greatly accentuated in this specific group. By testing all pregnant women and all TB patients in the health zone, 28% of all PLWHA could potentially be detected in a period of 33 months, showing its great potential in settings with a relatively low HIV prevalence
Health care-seeking behaviour and diagnostic delays for Human African Trypanosomiasis in the Democratic Republic of the Congo
No full textObjective About half of the patients with Human African trypanosomiasis (HAT) reported in the Democratic Republic of the Congo (DRC) are currently detected by fixed health facilities and not by mobile teams. Given the recent policy to integrate HAT control into general health services, we studied health seeking behaviour in these spontaneously presenting patients. Methods We took a random sample from all patients diagnosed with a first-time HAT episode through passive case finding between 1 October 2008 and 30 September 2009 in the two most endemic provinces of the DRC. Patients were approached at their homes for a structured interview. We documented patient delay (i.e. time between onset of symptoms and contacting a health centre) and health system delay (i.e. time between first contact and correct diagnosis of HAT). Results Median patient delay was 4 months (IQR 1-10 months, n = 66); median health system delay was 3 months (IQR 0.5-11 months). Those first presenting to public health centres had a median systems delay of 7 months (IQR 2-14 months, n = 23). On median, patients were diagnosed upon the forth visit to a health facility (IQR 3rd-7th visit). Conclusions Substantial patient as well as health system delays are incurred in HAT cases detected passively. Public health centres are performing poorly in the diagnostic work-up for HAT, mainly because HAT is a relatively rare disease with few and non-specific early symptoms. Integration of HAT diagnosis and treatment into general health services requires strong technical support and well-organized supervision and referral mechanisms
Mycobacteria in terrestrial small mammals on cattle farms in Tanzania
No full textThe control of bovine tuberculosis and atypical mycobacterioses in cattle in developing countries is important but difficult because of the existence of wildlife reservoirs. In cattle farms in Tanzania, mycobacteria were detected in 7.3% of 645 small mammals and in cow's milk. The cattle farms were divided into "reacting" and "nonreacting" farms, based on tuberculin tests, and more mycobacteria were present in insectivores collected in reacting farms as compared to nonreacting farms. More mycobacteria were also present in insectivores as compared to rodents. All mycobacteria detected by culture and PCR in the small mammals were atypical mycobacteria. Analysis of the presence of mycobacteria in relation to the reactor status of the cattle farms does not exclude transmission between small mammals and cattle but indicates that transmission to cattle from another source of infection is more likely. However, because of the high prevalence of mycobacteria in some small mammal species, these infected animals can pose a risk to humans, especially in areas with a high HIV-prevalence as is the case in Tanzania
Validation of a four-primer real-time PCR as a diagnostic tool for single and mixed Plasmodium infections
No full textWhile microscopy remains the gold standard for malaria diagnosis, molecular tools gain more interest. To improve the detection of mixed-infections, we developed a four-primer real-time PCR with 4 Plasmodium species-specific forward primers, based on the pan-primer design with universal Plasmodium primers as described before. After validation for analytical sensitivity, specificity and reproducibility, the four-primer-PCR was evaluated on 351 blood samples from patients presenting at the outpatient clinic of the Institute of Tropical Medicine (Belgium). With the four-primer-PCR, we identified 188 Plasmodium falciparum, 54 P. vivax, 52 P. ovale and 13 P. malariae single infections, 27 mixed-infections (14 Pf+Pm; 12 Pf+Po; 1 Pv+Pm) and 17 negative specimens. Compared to the pan-primer-PCR, we observed lower Ct-values with a mean difference of 2.23, a higher analytical sensitivity (Pf/Pv: 0.02; Po 0.004; Pm: 0.006 asexual parasites/mul) and 15 extra mixed-infections. Compared to microscopy, we detected 17 extra mixed-infections and identified Plasmodium species in 4 microscopic-positive samples in which species identification was not possible. Additionally, the PCR corrected 13 species mismatches between P. ovale and P. vivax and detected 11 P. falciparum as a second species that was not identified by microscopy and in five of them not picked up by RDT. PCR confirmed the presence of P. falciparum in 30/46 HRP-2 positive samples that were microscopy negative. We conclude that the presently developed four-primer real-time PCR is complementary to standard malaria diagnostic tests in clinical laboratories with an added value for simultaneous identification of the four Plasmodium species and the detection of mixed-infections
How can disease control programs contribute to health systems strengthening in sub-Saharan Africa? Which health systems for disease control
No full textAn Interferon-gamma ELISPOT assay with two CTL epitopes derived from HTLV-1 Tax region 161-233 discriminates HAM/TSP patients from asymptomatic HTLV-1 carriers in a Peruvian population
No full textHTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic and progressive disorder caused by the human T-lymphotropic virus type 1 (HTLV-1). In HTLV-1 infection, a strong cytotoxic T cell (CTL) response is mounted against the immunodominant protein Tax. Previous studies carried out by our group reported that increased IFN-gamma enzyme-linked immunospot (ELISPOT) responses against the region spanning aminoacids 161 to 233 of the Tax protein were associated with HAM/TSP and increased HTLV-1 proviral load (PVL). An exploratory study was conducted on 16 subjects with HAM/TSP, 13 asymptomatic carriers (AC), and 10 HTLV-1-seronegative controls (SC) to map the HAM/TSP associated CTL epitopes within Tax region 161-233. The PVL of the infected subjects was determined and the specific CTL response was evaluated with a 6 h incubation IFN-gamma ELISPOT assay using peripheral blood mononuclear cells (PBMC) stimulated with 16 individual overlapping peptides covering the Tax region 161-233. Other pro-inflammatory and Th1/Th2 cytokines were also quantified in the supernatants by a flow cytometry multiplex assay. In addition, a set of human leukocyte antigen (HLA) class I alleles that bind with high affinity to the CTL epitopes of interest was determined using computational tools. Univariate analyses identified an association between ELISPOT responses to two new CTL epitopes, Tax 173-185, and Tax 181-193, and the presence of HAM/TSP as well as an increased PVL. The HLA-A*6801, which is predicted to bind to Tax 181-193 peptide, was over-presented in the HAM/TSP patients tested