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Steffen Borrmann

Publications and source records attributed to Steffen Borrmann.

14 recordsLinked to original sources
PubMed2026

Multiple local PfDHFR I164L haplotype expansions drive Plasmodium falciparum antifolate resistance in Uganda.

Mutations in the Plasmodium falciparum genes, pfdhfr and pfdhps, drive antifolate resistance and threaten malaria control in regions where sulfadoxine-pyrimethamine (SP) is the primary chemoprevention strategy. The spatial patterns and evolutionary dynamics of these mutations in high-transmission settings remain incompletely understood. Here we genotyped 11 resistance-associated mutations in pfdhfr and pfdhps in 4,725 P. falciparum isolates collected from 16 Ugandan health facilities as part of annual surveillance between 2016 and 2022. Notably, we show that the frequency of PfDHFR I164L, which confers higher pyrimethamine resistance, increased over time from 19.4% to 32.4%. Using identity-by-descent, haplotype structure, and extended haplotype homozygosity analyses, we show that PfDHFR I164L is present on multiple haplotype backgrounds and undergoes localised expansions, without detectable signatures of recent positive selection at all but one site. Our results suggest that the evolution of antifolate resistance, driven by PfDHFR I164L, is spatially heterogeneous and complex in regions that primarily use SP chemoprevention programmes.

Plasmodium falciparum↗
PubMed2004

Long-term treatment of intestinal helminths increases mite skin-test reactivity in Gabonese schoolchildren.

BACKGROUND: Several studies have shown an inverse association between helminth infections and atopy, but none have clearly established that the pathogens themselves, rather than other associated factors, cause the suppression of atopy. To show a direct link, prospective intervention studies are required. METHODS: A randomized, controlled trial was performed to study whether repeated anthelminthic treatment results in increased allergic sensitivity to house dust mites (HDMs) in chronically infected children. The trial population consisted of 317 Gabonese schoolchildren with a high prevalence of intestinal helminths. Intervention consisted of treatment every 3 months with praziquantel and mebendazole and with placebo in the control group. Follow-up lasted 30 months: at 6-month intervals, skin-test sensitivity to mites, helminth infection status, and levels of total IgE were determined. RESULTS: Treatment resulted in a significant increase in the rate of developing skin sensitivity to HDMs (hazard ratio, 2.51; 95% confidence interval, 1.85-3.41), which was mediated, in part, by reductions in Ascaris and/or Trichuris infections. Levels of total IgE were reduced, but this did not mediate the effect of treatment on skin-test reactivity. CONCLUSIONS: Anthelminthic treatment of chronically infected children results in increased atopic reactivity, which indicates that helminths directly suppress allergic reactions.

Adolescent↗
PubMed2004

Fosmidomycin-clindamycin for Plasmodium falciparum Infections in African children.

BACKGROUND: Fosmidomycin is a new antimalarial drug with a novel mechanism of action. Studies in Africa that have evaluated fosmidomycin as monotherapeutic agent demonstrated its excellent tolerance, but 3-times-daily treatment regimens of >or=4 days were required to achieve radical cure, prompting further research to identify and validate a suitable combination partner to enhance its efficacy. METHODS: We conducted a randomized, controlled, open-label study to evaluate the efficacy and safety of fosmidomycin combined with clindamycin (n=12; 30 and 5 mg/kg body weight every 12 h for 5 days, respectively), compared with fosmidomycin alone (n=12; 30 mg/kg body weight every 12 h for 5 days) and clindamycin alone (n=12; 5 mg/kg body weight every 12 h for 5 days) for the clearance of asymptomatic Plasmodium falciparum infections in schoolchildren in Gabon aged 7-14 years. RESULTS: Asexual parasites were rapidly cleared in children treated with fosmidomycin-clindamycin (median time, 18 h) and fosmidomycin alone (25 h) but slowly in children treated with clindamycin alone (71 h; P=.004). However, only treatment with fosmidomycin-clindamycin or clindamycin alone led to the radical elimination of asexual parasites as measured by day 14 and 28 cure rates of 100%. Asexual parasites reappeared by day 28 in 7 children who received fosmidomycin (day 14 cure rate, 92% [11/12; day 28 cure rate, 42% [5/12]). All regimens were well tolerated, and no serious adverse events occurred. CONCLUSION: The combination of fosmidomycin and clindamycin is well tolerated and superior to either agent on its own with respect to the rapid and radical clearance of P. falciparum infections in African children.

Antimalarials↗
PubMed2003

Atovaquone and proguanil versus amodiaquine for the treatment of Plasmodium falciparum malaria in African infants and young children.

Malaria-related morbidity and mortality are greatest among young children in areas with high malaria transmission intensity. An open-label, randomized study was done to evaluate the efficacy and safety of the combination of atovaquone and proguanil formulated as pediatric-strength tablets (20 and 8 mg/kg of body weight, respectively, administered once daily for 3 days), compared with amodiaquine (10 mg/kg of body weight, once daily for 3 days), among children weighing > or =5 and <11 kg in Gabon. Two hundred patients aged 3-43 months were recruited. Use of atovaquone/proguanil resulted in a cure rate on day 28 of 95% (87 of 92 children), compared with 53% (41 of 78 children) for amodiaquine (difference, 42%; 95% CI, 30%-54%; P<.001). The incidence of adverse events was similar in both groups, and no serious adverse events were attributed to the use of atovaquone/proguanil. Atovaquone/proguanil was found to be highly effective and safe for the treatment of Plasmodium falciparum malaria in infants and young children weighing 5-10 kg in Africa.

Amodiaquine↗
PubMed2003

Antibody responses to Plasmodium falciparum merozoite surface protein-1 and efficacy of amodiaquine in Gabonese children with P. falciparum malaria.

The relationship between the efficacy of amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria and preexisting antibodies against merozoite surface protein (MSP)-1, a blood-stage P. falciparum antigen, was investigated. The immunoglobulin G antibody response to different MSP-1 recombinant proteins was evaluated in plasma samples from Gabonese children with uncomplicated malaria who were treated with amodiaquine. The prevalence of anti-MSP-1 antibodies was similar among patients with either parasitological and clinical cure after treatment (n=102) or treatment failure (n=51) by day 28 (83% in both groups). However, associations between antibody responses to K1 and MAD20 allelic families and therapeutic success were found (P< .001 and P= .034, respectively). A high proportion of plasma samples recognizing several antigens was found in the cured group. This association was significant even when data were stratified by age, particularly for the K1 family antigens (P= .029). These results suggest that humoral immune responses play a supportive role in the efficacy of amodiaquine treatment.

Amodiaquine↗
PubMed2003

Severe malaria in a splenectomised Gabonese woman.

BACKGROUND: The intact splenic function is of utmost importance for the host's defence capacity against Plasmodium spp. not only by limiting the acute infection through the removal of parasites from the blood stream, but also by modulating parasite antigen expression on the surface of infected red blood cells as well as cellular and humoral immune response. Splenectomised individuals are at high risk to develop a more severe and prolonged disease, even if they had acquired semi-immunity prior to their loss of splenic tissue. CASE REPORT: We report on a 37 year old splenectomised Gabonese woman who developed severe falciparum malaria with hyperparasitaemia, profound anaemia, and an overwhelming gametocytaemia, recovering very slowly following quinine therapy. Whereas the clinical course is not at odds with previous descriptions, the massive occurrence of mature gametocytes as documented here has not been reported before. Whether the high gametocyte count observed in our patient was primarily due to the impaired clearance of asexual forms or to the induction of gametocytogenesis remains unclear. Regarding the optimal drug regimen for treating malaria in splenectomized patients, a combination of an aminoquinoline with an artemisinin derivative might be the optimal choice.

Adult↗
PubMed2003

Short-course artesunate treatment of uncomplicated Plasmodium falciparum malaria in Gabon.

Artesunate is one of the most important antimalarial agents available, since it is effective against parasites that have developed resistance to conventional antimalarials in sub-Saharan Africa. Antimalarial combination chemotherapies with artesunate (4 mg/kg of body weight once daily for 3 days) as one partner have been proposed. However, the efficacy of a 3-day course of artesunate alone has never been evaluated in individuals in Africa (which has 90% of the worldwide malaria burden) living in regions of hyperendemicity, where a considerable degree of immunity might substantially enhance the efficacy of short courses of artesunate compared to those in regions where the levels of endemicity are low. This lack of information does not permit a systematic assessment of the value of artesunate-based combination chemotherapies in Africa. Therefore, we studied the efficacy and safety of a 3-day course of artesunate (4 mg/kg of body weight, orally, once daily) for the treatment of uncomplicated Plasmodium falciparum malaria in Gabonese patients aged 4 to 15 years (n = 50). Artesunate was well tolerated, and no severe adverse event was reported. Parasite elimination was rapid and was achieved in all patients within < or =72 h (geometric mean time to elimination, 34 h). The PCR-corrected cure rate by day 14 was 92% (46 of 50 patients), but it dropped to 72% (36 of 50 patients) by day 28. We conclude that a 3-day course of artesunate fails to achieve sufficiently high cure rates for uncomplicated falciparum malaria in Gabonese children.

Adolescent↗
PubMed2002

Fosmidomycin for malaria.

Safe and effective antimalarial drugs with new methods of action are urgently needed. Fosmidomycin inhibits the synthesis of isoprenoid by Plasmodium falciparum, and suppresses the growth of multidrug-resistant strains in vitro. Our aim was to assess the efficacy and tolerability of fosmidomycin in adults with malaria in Gabon. We administered the drug for 5, 4, or 3 days (1.2 g every 8 h), in nine, eight, and ten evaluable patients, respectively. All treatment regimens were well tolerated. Cure rates by day 14 were 89% (eight of nine), 88% (seven of eight), and 60% (six of ten), for treatment durations of 5, 4, and 3 days, respectively. These data suggest that fosmidomycin is a safe and effective treatment for uncomplicated malaria if given for 4 days or more.

Adult↗
PubMed2002

Fosmidomycin for the treatment of malaria.

In malaria parasites, isoprenoids are synthesised by the mevalonate independent 1-deoxy- D-xylulose 5-phosphate (DOXP) pathway. Fosmidomycin, a natural antibiotic originally developed for the treatment of bacterial infections, represents an inhibitor of DOXP reductoisomerase, an essential enzyme of this pathway. In recent clinical studies it was shown that fosmidomycin is effective in curing uncomplicated Plasmodium falciparum malaria in humans. The treatment was well tolerated and resulted in a fast parasite and fever clearance. However, the high rate of recrudescence precludes the use of fosmidomycin as a monotherapy. In drug combination studies, synergy of fosmidomycin with clindamycin was observed. Clinical studies with a fosmidomycin-clindamycin combination are currently ongoing.

Animals↗
PubMed2002

Immune responses induced by repeated treatment do not result in protective immunity to Schistosoma haematobium: interleukin (IL)-5 and IL-10 responses.

The hypothesis that repeated treatments enhance acquired immunity against schistosomes by stimulating strong T helper 2 responses was tested. Schistosoma haematobium-infected schoolchildren were monitored for 3 years. During the first 2 years, children who did not receive chemotherapy were compared with those treated once or repeatedly. After specific immune responses were measured at 24 months, praziquantel was given to all children to clear any schistosome infections. Twelve months later, the infection status of the children was determined and compared with cytokine profiles at month 24, to gain insight into which immunologic profiles can predict resistance or susceptibility to schistosome infections. Repeated treatment led to high specific levels of interleukin (IL)-5 and low interferon-gamma production but did not protect against reinfection. After adjusting for variables, such as sex, age, and infection status at study onset, high levels of parasite-specific IL-10 were a risk factor for reinfection, and high levels of IL-5 were associated with hematuria development.

Adolescent↗
PubMed2002

Age-dependent enhancement of IFN-gamma responses to Plasmodium falciparum liver stage antigen-1 T cell epitopes.

We assessed the cellular immunological responses to two Plasmodium falciparum liver-stage antigen (LSA)-1-derived T-cell epitopes in healthy Gabonese children and adults. The N-terminal peptide, designated T1, induced interferon (IFN)-gamma production in peripheral blood mononuclear cells (PBMC) from a significantly lower proportion of children compared to adults, but both interleukin (IL)-10 and IL-12 were produced by similar proportions of PBMC from the two groups. The LSA-1 junction region peptide (LSA-J) also induced IFN-gamma in a lower, but in this case statistically non-significant, proportion of PBMC from children compared to adults, whilst the proportions producing either IL-10 or IL-12 were again similar. Higher amounts of both IFN-gamma and IL-10 were induced by LSA-J compared to T1. CD8+ T-cells were shown to be primarily responsible for the production of peptide-driven IFN-gamma. The results suggest a significant age-related increase in the proportion of individuals capable of producing IFN-gamma to the N-terminal T1 epitope, with a shift from a predominantly IL-10-led response in children.

Adolescent↗
PubMedDate not supplied

Severe malarial anemia associated with increased soluble Fas ligand (sFasL) concentrations in Gabonese children.

To investigate if severe malarial anemia is associated with specific cytokine overproduction, we evaluated serum levels of soluble Fas ligand (sFasL), tumor necrosis factor (TNF-alpha) and interleukin-10 (IL-10) from three groups of young children with Plasmodium falciparum infection (asymptomatic cases, uncomplicated malaria cases and severe malarial anemia cases), in a hyperendemic area of Gabon. In uncomplicated cases, only TNF levels were significantly (p < 0.001) increased in comparison to asymptomatic cases with P. falciparum infection. High levels of sFasL, TNF-alpha and IL-10 were associated with low hemoglobin concentrations, sFasL levels were significantly higher in children with severe malarial anemia (p < 0.001) as compared to both other groups. The parasite density was positively correlated with IL-10, TNF-alpha and sFasL levels. TNF-alpha and sFasL, but not IL-10 or parasitemia, were independent predictors of hemoglobin concentrations. These results suggest that, in malaria, a specific dysregulation of the cytokine balance may lead to complications such as severe anemia.

Acute Disease↗