Towards Point-of-Care Diagnostic and Staging Tools for Human African Trypanosomiaisis

Matovu, Enock; Kazibwe, Anne; Mugasa, Claire M.; Ndung’u, Joseph Mathu; Njiru, Zablon Kithingi

doi:10.1155/2012/340538

Cited by 20 publications

(12 citation statements)

References 58 publications

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“…Because of its simplicity, rapidity, and versatility in readout options, LAMP offers a distinct advantage over other molecular diagnostic methods for use in the field. LAMP test kits are now commercially available or in development for the detection of Mycobacterium tuberculosis complex [50], and human African trypanosomiasis [52] for use in resource-limited settings.…”

Section: Introductionmentioning

confidence: 99%

Diagnosis of Brugian Filariasis by Loop-Mediated Isothermal Amplification

et al. 2012

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In this study we developed and evaluated a Brugia Hha I repeat loop-mediated isothermal amplification (LAMP) assay for the rapid detection of Brugia genomic DNA. Amplification was detected using turbidity or fluorescence as readouts. Reactions generated a turbidity threshold value or a clear visual positive within 30 minutes using purified genomic DNA equivalent to one microfilaria. Similar results were obtained using DNA isolated from blood samples containing B. malayi microfilariae. Amplification was specific to B. malayi and B. timori, as no turbidity was observed using DNA from the related filarial parasites Wuchereria bancrofti, Onchocerca volvulus or Dirofilaria immitis, or from human or mosquito. Furthermore, the assay was most robust using a new strand-displacing DNA polymerase termed Bst 2.0 compared to wild-type Bst DNA polymerase, large fragment. The results indicate that the Brugia Hha I repeat LAMP assay is rapid, sensitive and Brugia-specific with the potential to be developed further as a field tool for diagnosis and mapping of brugian filariasis.

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Section: Introductionmentioning

confidence: 99%

Diagnosis of Brugian Filariasis by Loop-Mediated Isothermal Amplification

et al. 2012

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“…In addition, parasitaemia in the relapsed monkeys did not reach the peak levels observed in primary parasitaemia ( Fig. 5 ) and was more comparable to the pattern observed in T. b. gambiense infections in vervet monkeys [ 33 ] (unpublished data, TRC-KARI); human T. b. gambiense infections, which comprise more than 95% of HAT, are similarly characterised by very low parasitaemias [ 3 , 34 , 35 ]. Our study did not elucidate the factors responsible for the generally lower parasite loads detected in the blood of relapse as compared to primary infections in the same monkeys.…”

Section: Discussionmentioning

confidence: 67%

“…Although WBC changes exhibited wide variations, the finding that WBC remained elevated in monkeys that eventually relapsed, suggests that it could be investigated further as a potential surrogate marker for cure assessment in this model. Other potential surrogate tests for cure assessment include WBC counts in CSF [ 38 ], serum/plasma trypanosome antigen levels as determined using TrypTECTT CIAT [ 23 ], HAT ELISA [ 39 ], and a variety of DNA-based polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) techniques [ 40 , 41 ]. However, all these surrogate tests require validation to be used as biomarkers of cure/relapse in drug trials.…”

Section: Discussionmentioning

confidence: 99%

Chemotherapy of Second Stage Human African Trypanosomiasis: Comparison between the Parenteral Diamidine DB829 and Its Oral Prodrug DB868 in Vervet Monkeys

et al. 2015

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Human African trypanosomiasis (HAT, sleeping sickness) ranks among the most neglected tropical diseases based on limited availability of drugs that are safe and efficacious, particularly against the second stage (central nervous system [CNS]) of infection. In response to this largely unmet need for new treatments, the Consortium for Parasitic Drug Development developed novel parenteral diamidines and corresponding oral prodrugs that have shown cure of a murine model of second stage HAT. As a rationale for selection of one of these compounds for further development, the pharmacokinetics and efficacy of intramuscular (IM) active diamidine 2,5-bis(5-amidino-2-pyridyl)furan (DB829; CPD-0802) and oral prodrug2,5-bis[5-(N-methoxyamidino)-2-pyridyl]furan (DB868) were compared in the vervet monkey model of second stage HAT. Treatment was initiated 28 days post-infection of monkeys with T. b. rhodesiense KETRI 2537. Results showed that IM DB829 at 5 mg/kg/day for 5 consecutive days, 5 mg/kg/day every other day for 5 doses, or 2.5 mg/kg/day for 5 consecutive days cured all monkeys (5/5). Oral DB868 was less successful, with no cures (0/2) at 3 mg/kg/day for 10 days and cure rates of 1/4 at 10 mg/kg/day for 10 days and 20 mg/kg/day for 10 days; in total, only 2/10 monkeys were cured with DB868 dose regimens. The geometric mean plasma Cmax of IM DB829 at 5 mg/kg following the last of 5 doses was 25-fold greater than that after 10 daily oral doses of DB868 at 20 mg/kg. These data suggest that the active diamidine DB829, administered IM, should be considered for further development as a potential new treatment for second stage HAT.

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“…Fortunately, recent innovations in the diagnostic technology for HAT show there might be cause for optimism. A rapid diagnostic test for HAT is now available [23] , [24] , molecular tools such as LAMP (loop-mediated isothermal amplification) are being evaluated for their potential use as confirmatory tests [25] and a proof of concept has been delivered on the use of certain biomarkers for staging of HAT [26] .…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Work-Up of Neurological Syndromes in a Rural African Setting: Knowledge, Attitudes and Practices of Health Care Providers

et al. 2014

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BackgroundNeurological disorders of infectious origin are common in rural sub-Saharan Africa and usually have serious consequences. Unfortunately, these syndromes are often poorly documented for lack of diagnostic tools. Clinical management of these diseases is a major challenge in under-equipped rural health centers and hospitals. We documented health care provider knowledge, attitudes and practices related to this syndrome in two rural health zones in Bandundu Province, Democratic Republic of Congo.MethodsWe used a qualitative research approach combining observation, in-depth interviews and focus group discussions. We observed 20 patient-provider contacts related to a neurological syndrome, conducted 12 individual interviews and 4 focus group discussions with care providers. All interviews were audiotaped and the transcripts were analyzed with the software ATLAS.ti.ResultsCare providers in this region usually limit their diagnostic work-up to clinical examination primarily because of the financial hurdles in this entirely out-of-pocket payment system. The patients prefer to purchase drugs rather than diagnostic tests. Moreover the general lack of diagnostic tools and the representation of the clinician as a “diviner” do not enhance any use of laboratory or other diagnostic methods.ConclusionInnovation in diagnostic technology for neurological disorders is badly needed in Central-Africa, but its uptake in clinical practice will only be a success if tools are simple, affordable and embedded in a patient-centered approach.

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Towards Point-of-Care Diagnostic and Staging Tools for Human African Trypanosomiaisis

Cited by 20 publications

References 58 publications

Diagnosis of Brugian Filariasis by Loop-Mediated Isothermal Amplification

Diagnosis of Brugian Filariasis by Loop-Mediated Isothermal Amplification

Chemotherapy of Second Stage Human African Trypanosomiasis: Comparison between the Parenteral Diamidine DB829 and Its Oral Prodrug DB868 in Vervet Monkeys

Diagnostic Work-Up of Neurological Syndromes in a Rural African Setting: Knowledge, Attitudes and Practices of Health Care Providers

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