Updated estimate of the duration of the meningo-encephalitic stage in gambiense human African trypanosomiasis

Checchi, Francesco; Funk, Sebastian; Chandramohan, Daniel; Haydon, Daniel T.; Chappuis, François

doi:10.1186/s13104-015-1244-3

Cited by 25 publications

(21 citation statements)

References 7 publications

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“…Passive case detection was assumed to occur at a fixed rate with individuals self-presenting to medical facilities after developing stage 2 disease; the rate was chosen such that individuals remain in stage 2 for six months on average. Whilst there is currently no robust estimate of this period, other modelling work has estimated that the duration of stage 2 disease is nine months on average in the absence of treatment [ 39 ]. In addition, it was assumed that there was some unknown level of underreporting of cases, due to either diagnosed cases not being entered into records or death before correct diagnosis (autopsies are not routinely performed to ascertain cause of death).…”

Section: Methodsmentioning

confidence: 99%

Quantitative evaluation of the strategy to eliminate human African trypanosomiasis in the Democratic Republic of Congo

et al. 2015

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BackgroundThe virulent vector-borne disease, Gambian human African trypanosomiasis (HAT), is one of several diseases targeted for elimination by the World Health Organization. This article utilises human case data from a high-endemicity region of the Democratic Republic of Congo in conjunction with a suite of novel mechanistic mathematical models to address the effectiveness of on-going active screening and treatment programmes and compute the likely time to elimination as a public health problem (i.e. <1 case per 10,000 per year).MethodsThe model variants address uncertainties surrounding transmission of HAT infection including heterogeneous risk of exposure to tsetse bites, non-participation of certain groups during active screening campaigns and potential animal reservoirs of infection.ResultsModel fitting indicates that variation in human risk of tsetse bites and participation in active screening play a key role in transmission of this disease, whilst the existence of animal reservoirs remains unclear. Active screening campaigns in this region are calculated to have been effective, reducing the incidence of new human infections by 52–53 % over a 15-year period (1998–2012). However, projections of disease dynamics in this region indicate that the elimination goal may not be met until later this century (2059–2092) under the current intervention strategy.ConclusionsImprovements to active detection, such as screening those who have not previously participated and raising overall screening levels, as well as beginning widespread vector control in the area have the potential to ensure successful and timely elimination.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-015-1131-8) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Quantitative evaluation of the strategy to eliminate human African trypanosomiasis in the Democratic Republic of Congo

et al. 2015

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“…Each candidate value of λ i was evaluated with 100 different random numbers of detected cases after correcting for misclassification, in 1,000,000 runs for each of these samples. In every run, random values of p 1 and p 2 were sampled from log-normal distributions with mode and spread given previously derived estimates [ 22 ]. The likelihood of each value of λ i was evaluated by enumerating the proportion of model runs that yielded the correct (estimated) prevalence of stage 1 and stage 2 cases at the second screening session while maintaining S 1 ≥ 0 and S 2 ≥ 0 at all times during the run.…”

Section: Methodsmentioning

confidence: 99%

The impact of passive case detection on the transmission dynamics of gambiense Human African Trypanosomiasis

et al. 2018

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Gambiense Human African Trypanosomiasis (HAT), or sleeping sickness, is a vector-borne disease affecting largely rural populations in Western and Central Africa. The main method for detecting and treating cases of gambiense HAT are active screening through mobile teams and passive detection through self-referral of patients to dedicated treatment centres or hospitals. Strategies based on active case finding and treatment have drastically reduced the global incidence of the disease over recent decades. However, little is known about the coverage and transmission impact of passive case detection. We used a mathematical model to analyse data from the period between active screening sessions in hundreds of villages that were monitored as part of three HAT control projects run by Médecins Sans Frontières in Southern Sudan and Uganda in the late 1990s and early 2000s. We found heterogeneity in incidence across villages, with a small minority of villages found to have much higher transmission rates and burdens than the majority. We further found that only a minority of prevalent cases in the first, haemo-lymphatic stage of the disease were detected passively (maximum likelihood estimate <30% in all three settings), whereas around 50% of patients in the second, meningo-encephalitic were detected. We estimated that passive case detection reduced transmission in affected areas by between 30 and 50%, suggesting that there is great potential value in improving rates of passive case detection. As gambiense HAT is driven towards elimination, it will be important to establish good systems of passive screening, and estimates such as the ones here will be of value in assessing the expected impact of moving from a primarily active to a more passive screening regime.

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“…T. b. gambiense is currently responsible for 98% of HAT cases [5], with the highest disease burden in the Democratic Republic of Congo (DRC) where 37.5 million people were estimated to be at some level of risk of g-HAT between 2012 and 2016 [1,2]. Humans are the principal reservoir for g-HAT and the progressive disease course occurs in two stages: a hemolymphatic phase (stage 1 with a mean duration of around 18 months) with common signs and symptoms including fever, headache, pruritus, weakness, asthenia, anemia, and lymphadenopathy; and a meningo-encephalic stage (stage 2 with a mean duration of around 8 months) occurring when the parasites have crossed the blood-brain barrier with resulting sleep disturbances and neuropsychiatric symptoms that may lead to coma and death if left untreated [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Innovative Partnerships for the Elimination of Human African Trypanosomiasis and the Development of Fexinidazole

et al. 2020

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Human African Trypanosomiasis (HAT or sleeping sickness) is a life-threatening neglected tropical disease that is endemic in 36 sub-Saharan African countries. Until recently, treatment options were limited and hampered by unsatisfactory efficacy, toxicity, and long and cumbersome administration regimens, compounded by infrastructure inadequacies in the remote rural regions worst affected by the disease. Increased funding and awareness of HAT over the past two decades has led to a steady decline in reported cases (<1000 in 2018). Recent drug development strategies have resulted in development of the first all-oral treatment for HAT, fexinidazole. Fexinidazole received European Medicines Agency positive scientific opinion in 2018 and is now incorporated into the WHO interim guidelines as one of the first-line treatments for HAT, allowing lumbar puncture to become non-systematic. Here, we highlight the role of global collaborations in the effort to control HAT and develop new treatments. The long-standing collaboration between the WHO, Sanofi and the Drugs for Neglected Diseases initiative (Geneva, Switzerland) was instrumental for achieving the control and treatment development goals in HAT, whilst at the same time ensuring that efforts were led by national authorities and control programs to leave a legacy of highly trained healthcare workers and improved research and health infrastructure.

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Updated estimate of the duration of the meningo-encephalitic stage in gambiense human African trypanosomiasis

Cited by 25 publications

References 7 publications

Quantitative evaluation of the strategy to eliminate human African trypanosomiasis in the Democratic Republic of Congo

Quantitative evaluation of the strategy to eliminate human African trypanosomiasis in the Democratic Republic of Congo

The impact of passive case detection on the transmission dynamics of gambiense Human African Trypanosomiasis

Innovative Partnerships for the Elimination of Human African Trypanosomiasis and the Development of Fexinidazole

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