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Expert patients and AIDS care; a literature review on expert patient programmes in high-income countries, and an exploration of their relevance for HIV/AIDS care in low-income countries with severe human resource shortages
Comparison of molecular markers for strain typing of Leishmania infantum
The epidemiology of Leishmania infantum, the etiological agent of visceral leishmaniasis, is changing rapidly; hence powerful typing tools are required in order to monitor the parasite populations spreading and to adapt adequate control measures. We compared here the resolving power of four molecular methods at the zymodeme level: PCR-RFLP analysis of kDNA minicircles (kDNAPCR-RFLP) and antigen genes (cysteine proteinase b and major surface protease, cpb- and gp63PCR-RFLP), multilocus microsatellite typing (MLMT) and random amplification of polymorphic DNA (RAPD) were applied to samples of 25 L. infantum MON-1 strains obtained from different hosts (HIV+ patients, HIV- patients and dogs) coming from three Spanish foci: Madrid, Mallorca and Ibiza. While RAPD was not sufficiently resolving, the other three methods allowed genotyping within the zymodeme. KDNAPCR-RFLP and MLMT were the most discriminatory and appeared the most adequate for strain fingerprinting. In an eco-geographical context, cpbPCR-RFLP, MLMT and kDNAPCR-RFLP were all informative: they showed here a similar picture, with the existence of cluster(s) of isolates from the islands and other one(s) of mixed composition (Madrid and the islands). None of the markers revealed an association with the host type or the clinical form. In general, there was a significant correlation between each pair of distances calculated from the cpb, microsatellite and kDNA data, respectively, but visual inspection of the trees revealed a better congruence between cpb and microsatellite trees. The methods used here are complementary and each adapted to answer specific epidemiological questions. Their choice should be the result of a compromise between the required resolving power, the genetic features of the respective markers and the technical aspects
Tsetse fly saliva accelerates the onset of Trypanosoma brucei infection in a mouse model associated with a reduced host inflammatory response
Tsetse flies (Glossina sp.) are the vectors that transmit African trypanosomes, protozoan parasites that cause human sleeping sickness and veterinary infections in the African continent. These blood-feeding dipteran insects deposit saliva at the feeding site that enables the blood-feeding process. Here we demonstrate that tsetse fly saliva also accelerates the onset of a Trypanosoma brucei infection. This effect was associated with a reduced inflammatory reaction at the site of infection initiation (reflected by a decrease of interleukin-6 [IL-6] and IL-12 mRNA) as well as lower serum concentrations of the trypanocidal cytokine tumor necrosis factor. Variant-specific surface glycoprotein-specific antibody isotypes immunoglobulin M (IgM) and IgG2a, implicated in trypanosome clearance, were not suppressed. We propose that tsetse fly saliva accelerates the onset of trypanosome infection by inhibiting local and systemic inflammatory responses involved in parasite control
Safety and efficacy of dihydroartemisinin/piperaquine (Artekin) for the treatment of uncomplicated Plasmodium falciparum malaria in Rwandan children
In Rwanda, amodiaquine+sulfadoxine/pyrimethamine (AQ+SP) is the current first-line treatment for malaria, introduced in 2001 as an interim strategy before the future deployment of an artemisinin-based combination treatment (ACT). Dihydroartemisinin/piperaquine (DHA-PQP) is a new co-formulated and well tolerated ACT increasingly used in Southeast Asia where it has proved to be highly effective against Plasmodium falciparum malaria. We tested the efficacy, safety and tolerability of DHA-PQP in children with uncomplicated P. falciparum malaria. A randomised, open trial was carried out in 2003-2004. Seven hundred and sixty-two children aged 12-59 months with uncomplicated P. falciparum malaria were randomly allocated to one of the following treatments: amodiaquine+artesunate; AQ+SP; or DHA-PQP. Patients were followed-up until Day 28 after treatment. Adverse events and clinical and parasitological outcomes were recorded. Children treated with DHA-PQP or AQ+AS had a significantly higher cure rate compared with those treated with amodiaquine+sulfadoxine/pyrimethamine (95.2% and 92.0% vs. 84.7%, respectively). Parasite clearance was significantly faster in children treated with DHA-PQP and AQ+AS compared with those treated with amodiaquine+sulfadoxine/pyrimethamine. The frequency of adverse events was significantly lower in patients treated with DHA-PQP than in those treated with combinations containing amodiaquine. A 3-day treatment with DHA-PQP proved to be efficacious with a good safety and tolerability profile and could be a good candidate for the next first-line treatment
Safety and efficacy of lumefantrine-artemether (Coartem) for the treatment of uncomplicated Plasmodium falciparum malaria in Zambian adults
BACKGROUND: In Zambia, unacceptably high resistance to commonly used antimalarial drugs prompted the choice of artemether-lumefantrine (AL) as first line treatment for uncomplicated Plasmodium falciparum malaria. Although the safety and efficacy of AL have been extensively documented, no clinical trials had been carried out in Zambia. METHODS: Nine hundred seventy one adult patients with uncomplicated malaria were randomized to either sulfadoxine-pyrimethamine (SP)(486) or AL (485) and followed up for 45 days. Outcome of treatment was defined according to the standard WHO classification. Recurrent parasitaemia were genotyped to distinguish between recrudescence and new infection. RESULTS: Fever at day 3 was significantly lower (AL: 0.9%; 4/455; SP: 3,5%; 15/433; p = 0.007) and the mean haemoglobin at day 45 significantly higher (AL: 134 g/l; SP 130 g/l; p = 0.02) in the AL group. Almost all clinical symptoms cleared faster with AL. Early treatment failure was significantly higher in the SP (25/464) than in the AL (2/463) (OR: 13.1 95% CI: 3.08-55.50; P < 0.001). The rate of new infections was similar in both groups (18 with SP and 19 with AL). Late clinical failure (OR: 2.55; 95% CI: 1.34-4.84; P = 0.004) and late parasitological failure (OR:3.18; 95% CI: 1.25-8.09; P = 0.02) were significantly higher in the SP group. Total treatment failure was significantly higher in the SP group (96/393; 19.3%) as compared to the AL (22/403; 5.4%) group (OR: 4.15; 95% CI: 2.52-6.83; P < 0.001). CONCLUSION: In Zambia, the new first line regimen AL is far more efficacious than SP in treating uncomplicated P. falciparum malaria in adults. Data on safety and efficacy of AL in pregnant women are urgently needed
PCR techniques in diagnosis of human African trypanosomiasis: limits and epidemiological considerations
East Coast fever and multiple El Niño Southern oscillation ranks
East Coast fever (ECF), a tick-borne disease of cattle, is a major constraint to livestock development in Africa in general and southern Zambia in particular. Understanding the transmission patterns of this disease complex is very difficult as shown by previous studies in southern and eastern Zambia due to the interplay of risk factors. In this long-term study, we investigated whether global weather changes had any influence on disease transmission in traditionally kept cattle in southern Zambia. The results from this study show a strong association between increased Theileria parva contacts in cattle and the presence of El Niño, clearly linking a simple climatic index to disease outbreaks. We therefore propose that in southern Zambia, the simple and readily available multiple El Niño Southern oscillation index (MEI) ranks be used in planning ECF control programmes and early warning
A Bayesian approach for the evaluation of six diagnostic assays and the estimation of Cryptosporidium prevalence in dairy calves
The prevalence of Cryptosporidium in calves and the test properties of six diagnostic assays (microscopy (ME), an immunofluorescence assay (IFA), two ELISA and two PCR assays) were estimated using Bayesian analysis. In a first Bayesian approach, the test results of the four conventional techniques were used: ME, IFA and two ELISA. This four-test approach estimated that the calf prevalence was 17% (95% Probability Interval (PI): 0.1-0.28) and that the specificity estimates of the IFA and ELISA were high compared to ME. A six-test Bayesian model was developed using the test results of the 4 conventional assays and 2 PCR assays, resulting in a higher calf prevalence estimate (58% with a 95% PI: 0.5-0.66) and in a different test evaluation: the sensitivity estimates of the conventional techniques decreased in the six-test approach, due to the inclusion of two PCR assays with a higher sensitivity compared to the conventional techniques. The specificity estimates of these conventional assays were comparable in the four-test and six-test approach. These results both illustrate the potential and the pitfalls of a Bayesian analysis in estimating prevalence and test characteristics, since posterior estimates are variables depending both on the data at hand and prior information included in the analysis. The need for sensitive diagnostic assays in epidemiological studies is demonstrated, especially for the identification of subclinically infected animals since the PCR assays identify these animals with reduced oocyst excretion, which the conventional techniques fail to identify