269 research outputs found
Improving the diagnostic work-up of neurological disorders in rural Central Africa
No full textAbstract: Neurological disorders are a complex of symptoms and signs related to the nervous system that may be due to a wide variety of etiologies. Most causative conditions can be severe if left untreated and contribute to the major global mortality and morbidity of this syndrome. In sub-Saharan Africa, the burden is even more considerable because of a wider spectrum of infections, substantial delays in management and lack of diagnostic facilities and specialized care. The main purpose of this PhD dissertation is to improve the diagnostic workup of neurological disorders in rural areas of the Democratic Republic of the Congo (DRC). A large prospective etiological and diagnostic study was conducted from 2012 to 2016 in 351 children > 5 years and adults presenting with a pre-defined set of neurological complaints at the \u201cH\uf4pital G\ue9n\ue9ral de R\ue9ference\u201d of Mosango, Kwilu province, DRC. This study on NDs in DRC was part of a larger multicentric research project, conducted by the NIDIAG (Neglected Infections DIAGnosis; htpps://nidiag.eu) consortium, that aimed at improving the diagnosis of Neglected Tropical/Infectious Diseases in challenging syndromes. Considering its main study purpose, this PhD thesis had three specific objectives: \u2022Firstly, to investigate the clinical spectrum, etiologies, and outcome of neurological disorders observed in the rural hospital of Mosango, DRC \u2022Then to assess the diagnostic performance and contribution of clinical symptoms, first-line laboratory results and novel point-of-care RDTs for the diagnosis of HAT and other priority NTDs/IDs in patients with neurological disorders in the rural hospital of Mosango \u2022Finally, to support the elaboration of an innovative integrated syndromic diagnostic tool (multi-disease approach) for neurological disorders, designed to first-line clinicians in rural DRC Reference diagnostic methods were systematically used for the diagnosis of a set of severe and treatable neuro-infections considered as priority conditions and for the field evaluation of new rapid diagnostic tests (RDTs). Pre-established clinical case definitions and post-hoc expert consensus were used for diagnostic ascertainment of the remaining etiologies. No neuroimaging was available in the study hospital. The core prospective study revealed that (i) the patterns of clinical presentation were very diverse; (ii) both infectious and noncommunicable etiologies had varied presentations; and (iii) the frequency of seven priority neuro-infections (Second-stage HAT, cerebral malaria, bacterial meningitis, CNS tuberculosis, neurosyphilis, HIV-related neurological disorders, cryptococcal meningitis in HIV-positive individuals) were respectively low (between 1 and 5% for each of these diagnoses). Death occurred in 8% of the patients and was more frequent in cases diagnosed with neuro-infection. An additional post-hoc analysis showed that about 13% of the patients enrolled with NDs had serological evidence of circulating Taenia solium antigen. This suggests, for the first time, that active neurocysticercosis might be endemic in this part of DRC and supports the need for additional neuroimaging studies. We demonstrated that lumbar puncture (LP), a key procedure to diagnose neuro-infections, but with which most first-line clinicians feel uncomfortable, was safe in the absence of neuroimaging, provided that the locally elaborated protocol was strictly adhered to. In particular, no major procedure-attributable adverse event was observed. Several predictors of cerebrospinal (CSF) pleocytosis (> 5 white blood cell/\ub5L), a surrogate marker for infectious meningo-encephalitis, were identified, such as fever, altered consciousness, HIV infection and positive screening serology for human African trypanosomiasis (HAT). The study findings may assist in the selection of a subgroup of patients who would benefit most a diagnostic LP, and to withhold this procedure when it might be too risky. An additional diagnostic study demonstrated that a novel Human African trypanosomiasis (HAT)- Sero K-SeT rapid diagnostic test (RDT) was highly sensitive 100% (95% confidence interval: 67.6 to 100.0%) and specific 97% (95% confidence interval: 94.2% to 98.5%), with similar performance to that of the card agglutination test for trypanosomiasis (CATT), the currently routinely used screening assay. The high sensitivity and ease of use of this new RDT allows its current deployment in the most remote heath centers as screening tool for both clinical care and control activities. A post-hoc analysis evaluated the potential value of two bacterial biomarkers (C-reactive protein, CRP and procalcitonin, PCT) for the diagnosis of invasive bacterial infection (defined as bacterial meningitis or bacteremia or severe pneumonia; n=19 in the study population). Areas under the curve were 94.3% and 91.7% for CRP and PCT, respectively. More importantly, no single case of invasive bacterial infection was observed when the CRP value was normal (<10 mg/ml), suggesting that this biomarker, if available at the point of care at this cutoff, could reduce immediate antibiotic treatment in a substantial number of neurological patients who do not need it. This research has generated important knowledge on the pre-test probabilities of priority neuro-infections (in other words the frequencies of these diseases) among patients with NDs in the rural hospital of DRC. This has been translated in a preliminary diagnostic panorama with not-to-miss diagnoses, which has been presented to, and welcomed by, first-line care workers in the field. Through the calculation of likelihood ratios, the confirming and excluding powers of several key clinical features, first-line laboratory results and RDTs could be estimated for each priority disease. All these data have been finally integrated in a new electronic panorama on NDs, with the key support of the IT service of ITM. The elaboration of this e-panorama is described step by step in the last manuscript which is now under submission. In the final Chapter, we discuss the perspectives and challenges related to several outputs of this thesis such as the programmatic adoption of the new HAT screening tool in clinical settings, the wider implementation of electronic formats of the elaborated panoramic aid and the improvement of neurological teaching and training in my Department of Neurology, University of Kinshasa, DRC
The pathway to sustainable elimination of Human African Trypanosomiasis in Democratic Republic of Congo
No full textAbstract: Human African Trypanosomiasis (HAT) is a vector-borne parasitic disease caused by two subspecies of Trypanosoma brucei (T. b.) pathogenic to humans ; T. b. rhodesiense, in the Eastern and Southern Africa and T. b. gambiense in Central and Western Africa. It is limited to sub-Saharan Africa, between latitudes 14N and 29S, within the limits of the geographical distribution of the tsetse fly of Glossina genus, that transmits the disease. About 97-98% of all cases are due to T. b. gambiense that causes the chronic form of the disease (gambiense HAT), concerned by this research thesis, while T. b. rhodesiense causes the acute form of the disease. Due to steady decreasing in cases number along the last two decades, Gambiense HAT (gHAT) has been targeted for elimination as public health problem (PHP) by 2020 and now it is targeted for elimination of transmission (EoT) by 2030. The Democratic Republic of the Congo (DRC) remains the most affected country; now that the evolution of the disease seems inexorable towards the elimination of gHAT in the country, considering the fact that this disease trend observed at the national level, is certainly not the same at the subnational level, we aim to evaluate the disease trend from the national level to the subnational level as well as the quality and coverage of gHAT control activities between 2000 and 2016. Regarding the objective to eliminate HAT, based on lessons learned from past successes and failures and from research, challenges have been identified for sustained elimination of gHAT. These challenges include diagnostic and therapeutic tools and strategies suitable for Primary Health Care (PHC) system and health facilities in remote areas where gHAT is most prevalent, maintaining the technical capacity and interest among health care workers, and raising public awareness, ensuring sufficient coverage of control activities, addressing the question of the animal and asymptomatic reservoir, implementing effective monitoring of gHAT elimination and cost-effective surveillance system to assure a sustainable elimination and diagnose promptly any risk of reemergence of disease. Our scientific work is mainly oriented towards improving diagnostic tools and detection/treatment strategies to address the issue of integrating gHAT control into PHC system, improving coverage of activities, and analyze current results toward gHAT elimination in DRC. The sharp decline in number of gHAT cases in DRC is aligned with the gHAT elimination objective. However trend of this disease is very variable from one region to another
Contribution to the improvement of the control of Buruli ulcer in the territory of Songololo : impact of the decentralization and integration of control activities in basic health services
No full text
Intermittent preventive treatment an option to prevent malaria in schoolchildren living in endemic area for malaria
No full text
Novel diagnostic tests for human African trypanosomiasis : what is their role in primary health care services?
No full textContribution to strategic decision making in human African trypanosomiasis control
No full textRESUME<p>La Trypanosomiase Humain Africaine (THA) demeure un problème de santé publique pour plusieurs pays en Afrique subsaharienne. Le contrôle de la THA est basé essentiellement sur la stratégie de dépistage actif suivi du traitement des personnes infectées. Le dépistage actif est réalisé par des unités mobiles spécialisées, bien que les services de santé fixes jouent un rôle important en détectant « passivement » des cas. Le dépistage reposait jadis sur la palpation ganglionnaire mais, depuis le développement du test d’agglutination sur carte (CATT), trois possibilités se sont offertes aux programmes de contrôle à savoir: i) continuer avec la palpation ganglionnaire ii) combiner la palpation ganglionnaire avec le CATT iii) recourir au CATT seul. Certains programmes comme celui de la République Démocratique du Congo (RDC) ont opté pour la combinaison en parallèle de la palpation ganglionnaire avec le CATT. Toute personne ayant une hypertrophie ganglionnaire cervicale et/ou un CATT positif est considéré comme suspecte de la THA. Elle sera soumise aux tests parasitologiques de confirmation à cause de la toxicité des médicaments anti-THA. Les tests parasitologiques classiques sont l’examen du suc ganglionnaire (PG), l’examen du sang à l’état frais (SF), la goutte épaisse colorée (GE). La sensibilité de cette séquence a été estimée insuffisante par plusieurs auteurs et serait à la base d’une grande perte de l’efficacité de la stratégie dépistage-traitement. D’autres techniques de concentration ont été développées comme la mini-Anion Exchange Concentration Technique (mAECT), la Centrifugation en Tube Capillaire (CTC) et le Quantitative Buffy Coat (QBC), mais ces techniques de concentration ne sont pas utilisées en routine. <p>En RDC, une interruption des activités de contrôle en 1990 a eu comme conséquence une réémergence importante de la maladie du sommeil. Depuis 1998 les activités de contrôle ont été refinancées de manière structurée. <p>Ce travail vise deux buts à savoir le plaidoyer pour la continuité des activités de contrôle et la rationalisation des stratégies de contrôle. Nous avons évalué l’évolution de la maladie du sommeil en rapport avec le financement, son impact sur les ménages ainsi que la communauté. L’exercice de rationalisation a porté sur les outils de dépistage et de confirmation. Nous avons d’abord évalué la validité des tests, leur faisabilité ainsi que les coûts et ensuite nous avons effectué une analyse décisionnelle formelle pour comparer les algorithmes de dépistage et pour les tests de confirmation.<p>Pendant la période de refinancement structurel de la lutte contre la THA en RDC (1998-2003), le budget alloué aux activités a été doublé lorsqu’on le compare à la période précédente (1993-1997). Le nombre des personnes examinées a aussi doublé mais par contre le nombre des nouveaux cas de THA est passé d’un pic de 26 000 cas en 1998 à 11 000 en 2003. Le coût par personne examinée a été de 1,5 US. Pendant cette période, les activités ont été financées par l’aide extérieure à plus de 95%. Cette subvention pourrait laisser supposer que l’impact de la THA au niveau des ménages et des communautés est réduit mais lorsque nous avons abordé cet aspect, il s’est avéré que le coût de la THA au niveau des ménages équivaut à un mois de leur revenu et que la THA fait perdre 2145 DALYs dans la communauté. L’intervention par la stratégie de dépistage-traitement a permis de sauver 1408 DALYs à un coût de 17 US and per case detected and saved was 300 US per DALY, putting the intervention in the class of “good value for money”. <p>The use of CATT alone as screening test emerged as the most efficient strategy for active case finding. The marginal gain when neck gland palpation is added is minor and is not compensated by the high cost of doing the parasitological confirmation test on a high number of suspected cases. The concentration methods have a good sensitivity and acceptable feasibility. Adding them to the classical tree improves its sensitivity with 29 % for CTC and with 42 % for mAECT. The cost of CTC was 0.76 US. Sensitivity of fresh blood examination was poor. The algorithm LNP-TBF-CTC-mAECT was the most efficient costing 277 Euro per life saved and a marginal cost effectiveness ratio of 125 Euro per supplementary life saved. The algorithm LNP-TBF-CATT titration with treatment of persons with a negative parasitology but a CATT positive at a dilution of 1/8 and more becomes competitive when HAT prevalence is high. <p>We conclude that it is possible in the current RDC context to reduce HAT prevalence on condition that control activities are not interrupted. Using an algorithm that includes CATT in active case finding and the combination LNP-TBF-CTC-mAECT is the most efficient with an efficacy of 80 %. Feasibility and efficacy may differ from one place to another because HAT is very focalized, so it is necessary to test this novel algorithm in another HAT focus on a pilot basis, before deciding on a policy change. Implementation of this algorithm will require additional financial resources and political commitment.<p><p>Doctorat en Sciences de la santé publiqueinfo:eu-repo/semantics/nonPublishe
De evolutionaire epidemiologie van schistosomiase in het Senegal Rivierbekken. Het koppelen van parasietgenetica met infectie en pathologie in de mens
No full textSchistosomiasis is a major poverty-related disease, infecting more than 200 million people in developing countries. More than 90% of them live in Sub-Saharan Africa. It is caused by infection with Schistosoma flatworms that reside in the vascular system of the definitive host. Freshwater snails are the intermediate hosts of schistosomes and essential for the completion of their life cycle. Praziquantel is currently the only recommended drug for treating all species of schistosomes. It is effective in killing adult schistosome worms, but does not kill immature schistosomes and so does not prevent reinfection. Therefore schistosomiasis continues to (re-)emerge. The main schistosomiasis-related pathology is caused by the accumulation of eggs in tissues, leading to a typical inflammatory reaction, which can develop into fibrosis of the liver or urinary bladder.
This doctoral thesis builds on the integration of parasite genetics and evolutionary biology with the epidemiology of schistosomiasis, the so called “evolutionary epidemiology”, in the Senegal River Basin (SRB) in Northern Senegal. In the late eighties, the construction of dams on the Senegal River induced ecological changes that resulted in a huge outbreak of Schistosoma mansoni, causing intestinal schistosomiasis. Few years after this outbreak, also the prevalence of S. haematobium, causing urinary schistosomiasis, and the prevalence of S. bovis, infecting livestock, increased greatly. Today, S. mansoni and S. haematobium are co-endemic in the SRB and around Lac de Guiers, resulting in mixed-infections in humans.
In the first part of this thesis, we studied the molecular epidemiology of Schistosoma haematobium across the SRB. Transmission dynamics of S. haematobium in the SRB may be influenced by the hybridisation between S. haematobium and S. bovis. Hybridisation events of Schistosoma species are reported with increasing frequency, but the consequences of these hybridisation events have yet to be fully explored. The introgression of new genes in parasites may affect their virulence, transmission and drug susceptibility. Chapter 2 describes the heterogeneous distribution of hybrids across villages in the lower and middle valley of the Senegal River. The majority of hybrids in the SRB showed a S. haematobium nuclear (ITS rDNA) and a S. bovis mitochondrial profile (cox1). Remarkably, the occurrence of S. haematobium x S. bovis hybrids was significantly associated with the prevalence of S. mansoni, but not with S. haematobium. In Chapter 3 we found that egg morphology appears of limited value to detect parasites with a hybrid ancestry. In contrast to experimental studies, all eggs resembled the typical S. haematobium egg type. Based on the results of 17 microsatellite markers (Chapter 4), the hybrid parasites with a S. haematobium nuclear ITS rDNA profile and a S. bovis mtDNA profile did not cluster apart from the ‘pure’ S. haematobium parasites. This indicates that hybrids are in “panmixis” with pure S. haematobium worms, but not with S. bovis: they form a random mating schistosome population, without mating restrictions in the next generation. No first generation hybrids were found. This indicates that, in nature, a strong species boundary between S. haematobium and S. bovis persists. In S. haematobium populations, transmission appeared restricted between villages across the SRB, in comparison to transmission between individual hosts. These findings on S. haematobium contrast with the high transmission potential of S. mansoni populations across the SRB, as previously published by our group. This difference between both species may be related to the presence and the genetic constitution of the intermediate snail host populations, or to their different colonisation history.
In the second part of the thesis we took a closer look at the evolutionary epidemiology of Schistosoma mansoni, at the scale of the individual host. We hypothesized that, in addition to host-related factors, parasite genetic variation may explain a significant part of the variation in disease phenotype. In Chapter 5, a highly significant association was found between allelic variation at the parasite locus L46951 and host infection intensity as well as bladder morbidity. It was hypothesized that this locus may be linked with parasite fecundity. We performed in vivo experiments (Chapter 6) to prove the causality of this association on a genetically diverse field strain of S. mansoni. Although we did not obtain sufficient biological replica, the experimental set-up was promising. Preliminary results suggested that each parasite genotype induces a specific disease phenotype in its vertebrate host.
A better understanding of the interactions and hybridisation between schistosome species in the SRB is crucial to improve control strategies. Elucidating the functional mechanism that leads to the association between parasite genetic variation and human disease may guide the development of new drugs and vaccines.status: Publishe
Emerg Infect Dis
No full textAccording to the World Health Organization, human African trypanosomiasis (HAT) (sleeping sickness) caused the loss of approximately 1.5 million disability-adjusted life years (DALYs) in 2002. We describe the effect of HAT during 2000-2002 in Buma, a rural community near Kinshasa in the Democratic Republic of Congo. We used retrospective questionnaire surveys to estimate HAT-related household costs and DALYs. The HAT outbreak in Buma involved 57 patients and affected 47 (21%) households. The cost to each household was equivalent to 5 months' income for that household. The total number of HAT-related DALYs was 2,145, and interventions to control HAT averted 1,408 DALYs. The cost per DALY averted was US $17. Because HAT has a serious economic effect on households and control interventions are cost-effective, considering only global burden of disease rankings for resource allocation could lead to misguided priority setting if applied without caution in HAT-affected countries
- …
