Forecasting Human African Trypanosomiasis Prevalences from Population Screening Data Using Continuous Time Models

To eliminate and eradicate gambiense human African trypanosomiasis (HAT), maximizing the effectiveness of active case finding is of key importance. The progression of the epidemic is largely influenced by the planning of these operations. This paper introduces and analyzes five models for predicting HAT prevalence in a given village based on past observed prevalence levels and past screening activities in that village. Based on the quality of prevalence level predictions in 143 villages in Kwamouth (DRC), and based on the theoretical foundation underlying the models, we consider variants of the Logistic Model—a model inspired by the SIS epidemic model—to be most suitable for predicting HAT prevalence levels. Furthe

Should I Get Screened for Sleeping Sickness? A Qualitative Study in Kasai Province, Democratic Republic of Congo

Active screening strategies are common disease control interventions in the context of poor and remote rural communities with no direct access to healthcare facilities. For such activities to be as effective as possible, it is necessary that they are well adapted to local socio-economic and cultural settings. Our aim was to gain insight into the barriers communities in the Kasai-Oriental province of the Democratic Republic of Congo experience in relation to their participation in active screening activities for African sleeping sickness. Participation rates seem to be especially low in this province compared to other endemic regions in the country. We found several important factors to be in play, a number of which could be addressed by adapting the operational procedures of the mobile teams that perform the active screening activities (e.g., improved confidentiality during the screening procedure). However, more profound considerations were found in the form of regional beliefs related to the treatment of the disease. Although not based on rational grounds, these prohibitions seem to pose a significant barrier in a person's decision to seek diagnosis and treatment. A better understanding of these prohibitions and their origin could lead to improved participation rates for sleeping sickness screening in Kasai-Oriental

Taenia solium Cysticercosis in the Democratic Republic of Congo: How Does Pork Trade Affect the Transmission of the Parasite?

Taenia solium is a parasite that can affect both humans and pigs, causing important economic losses in pig production and being the main cause of acquired epilepsy in endemic areas. However, the parasite has been neglected in many African countries and particularly in the Democratic Republic of Congo (DRC), where recent data are non-existent. The present study is part of a first initiative to assess whether cysticercosis is actually present in DRC and to estimate its potential economic and public health importance. Focusing our work on porcine cysticercosis, we demonstrated high prevalence figures of active infections in villages in a rural area of DRC and in markets in the city of Kinshasa. Moreover, the intensity of infection was higher in pigs sampled in villages as compared to pigs sampled on urban markets. Preliminary surveys conducted in parallel in both study sites suggest an effect of pork trade on the transmission of the parasite selecting highly infected pigs at village level

Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa.

BACKGROUND: In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa. METHODS: Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15-0.4 mg PQ base/kg for children aged 1-5 years and 0.15-0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6-11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box-Cox transformation power exponential and tested PQ doses of 1-15 mg base, selecting dosing groups based on calculated mg/kg PQ doses. RESULTS: From the Box-Cox transformation power exponential model, five age categories were selected: (i) 6-11 months (n = 39,886, 6.03%), (ii) 1-5 years (n = 261,036, 45.46%), (iii) 6-9 years (n = 20,770, 3.14%), (iv) 10-14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12-0.25), (ii) 0.21 (0.13-0.37), (iii) 0.25 (0.16-0.38), (iv) 0.26 (0.15-0.38) and (v) 0.27 (0.17-0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively. CONCLUSIONS: We plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 - 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination

A Phase III Diagnostic Accuracy Study of a Rapid Diagnostic Test for Diagnosis of Second-Stage Human African Trypanosomiasis in the Democratic Republic of the Congo

Objectives: To estimate the diagnostic accuracy of HAT Sero K-SeT for the field diagnosis of second-stage human African trypanosomiasis (HAT). Design: A phase III diagnostic accuracy design. Consecutive patients with symptoms clinically suggestive of HAT were prospectively enrolled. We compared results of the index test HAT Sero K-SeT with those of a composite reference standard: demonstration of trypanosomes in cerebrospinal fluid (CSF), or trypanosomes detected in any other body fluid AND white blood cell count in CSF >5/μl. Setting: Rural hospital in the Democratic Republic of the Congo. Participants: All patients above five years old presenting at Mosango hospital with a neurological problem of recent onset at the exclusion of trauma. Interventions: n.a. Main Outcome Measures: Sensitivity and specificity of HAT Sero K-SeT test. Results: The sensitivity of the HAT Sero K-SeT was 8/8 or 100.0% (95% confidence interval: 67.6 to 100.0%) and the specificity was 258/266 or 97.0% (94.2% to 98.5%). Conclusion: The high sensitivity of the HAT Sero K-SeT is in line with previously published estimates, though the sample of HAT cases in this study was small. The specificity estimate was very high and precise. This test, when negative, allows the clinician to rule out HAT in a clinical suspect in a hospital setting in this endemic region

High frequency of Taenia solium antigen positivity in patients admitted for neurological disorders in the Rural Hospital of Mosango, Democratic Republic of Congo

Background The epidemiology of human cysticercosis and neurocysticercosis, caused by the larval stage of the pork tapeworm Taenia solium, is not well known in the Democratic Republic of Congo (DRC). Within a multicenter etiological and diagnostic study conducted by the NIDIAG consortium (“Better Diagnosis for Neglected Infections”) and investigating several challenging syndromes, we consecutively evaluated from 2012 to 2015 all patients older than 5 years presenting with neurological disorders (neurology cohort) and with fever > 7 days (persistent fever cohort) at the rural hospital of Mosango, province of Kwilu, DRC. In both cohorts, etiological diagnosis relied on a systematic set of reference laboratory assays and on pre-established clinical case definitions. No neuroimaging was available in the study hospital. In this study, we determined the frequency of T. solium infection in both cohorts and explored in the neurology cohort its association with specific neurological presentations and final etiological diagnoses. Methods We conducted a post-hoc descriptive and analytic study on cysticercosis in the neurology and persistent fever cohorts, based on the presence in serum samples of circulating T. solium antigen using the B158/B60 enzyme-linked immunosorbent assay (ELISA) and of cysticercosis IgG using the LDBIO Cysticercosis Western Blot IgG assay. Results For the neurology cohort, 340 samples (of 351 enrolled patients) were available for analysis (males: 46.8%; mean age: 38.9 years). T. solium antigen positivity was found in 43 participants (12.6%; 95% confidence interval [CI] 9.3–16.7%), including 9 of 60 (15%) patients with epilepsy. Among the 148 samples available from the persistent fever cohort (males: 39.9%; mean age: 19.9 years), 7 were positive in the T. solium antigen ELISA (4.7%; 95% CI 1.9–9.5%; P = 0.009 when compared to the neurology cohort). No significant association was found within the neurology cohort between positivity and clinical presentation or final diagnoses. Of note, the IgG antibody-detecting assay was found positive in only four (1.3%) of the participants of the neurology cohort and in none of the persistent fever cohort. Conclusions T. solium antigen positivity was found in at least 10% of patients admitted with neurological disorders in the Kwilu province, DRC, with no specific pattern of presentation. Further neuroimaging studies should be used to confirm whether neurocysticercosis is prevalent in this region

Where there is no brain imaging: Safety and diagnostic value of lumbar puncture in patients with neurological disorders in a rural hospital of Central Africa.

Analysis of cerebrospinal fluid (CSF) obtained by lumbar puncture (LP) is an essential step for the diagnostic approach of neurological disorders, in particular neuro-infections. In low-resource settings, it is even often the only available diagnostic method. Despite its key contribution, little is known on the risks and benefits of LP in the large tropical areas where hospital-based neuroimaging is not available. The objectives of this study were to assess the safety and diagnostic yield of LP in a rural hospital of central Africa and to identify predictors of CSF pleocytosis (white blood cell count >5/μL) as surrogate marker of neuro-infections. From 2012 to 2015, 351 patients admitted for neurological disorders in the rural hospital of Mosango, Kwilu province, Democratic Republic of Congo, were evaluated using a systematic clinical and laboratory workup and a standard operating procedure for LP. An LP was successfully performed in 307 patients (87.5%). Serious post-LP adverse events (headache, backache or transient confusion) were observed in 23 (7.5%) of them but were self-limiting, and no death or long-term sequelae were attributable to LP. CSF pleocytosis was present in 54 participants (17.6%), almost always associated with neuro-infections. Presenting features strongly and independently associated with CSF pleocytosis were fever, altered consciousness, HIV infection and positive screening serology for human African trypanosomiasis. In conclusion, the established procedure for LP was safe in this hospital setting with no neuroimaging and CSF analysis brought a substantial diagnostic contribution. A set of presenting features may help accurately selecting the patients for whom LP would be most beneficial

Histogram of estimated carrying capacities for the 143 villages in Kwamouth, as estimated by the LMCCC model.

<p>Measured as a percentage of the population.</p

Time needed to reach elimination in a “typical village” (current prevalence level of 5/1000), for different levels of the case detection fraction (<i>p</i> ⋅ <i>s</i>) and different screening intervals.

<p>Time needed to reach elimination in a “typical village” (current prevalence level of 5/1000), for different levels of the case detection fraction (<i>p</i> ⋅ <i>s</i>) and different screening intervals.</p