Connected diagnostics: linking digital rapid diagnostic tests and mobile health wallets to diagnose and treat brucellosis in Samburu, Kenya.

BACKGROUND: Despite WHO guidelines for testing all suspected cases of malaria before initiating treatment, presumptive malaria treatment remains common practice among some clinicians and in certain low-resource settings the capacity for microscopic testing is limited. This can lead to misdiagnosis, resulting in increased morbidity due to lack of treatment for undetected conditions, increased healthcare costs, and potential for drug resistance. This is particularly an issue as multiple conditions share the similar etiologies to malaria, including brucellosis, a rare, under-detected zoonosis. Linking rapid diagnostic tests (RDTs) and digital test readers for the detection of febrile illnesses can mitigate this risk and improve case management of febrile illness. METHODS: This technical advance study examines Connected Diagnostics, an approach that combines the use of point-of-care RDTs for malaria and brucellosis, digitally interpreted by a rapid diagnostic test reader (Deki Reader) and connected to mobile payment mechanisms to facilitate the diagnosis and treatment of febrile illness in nomadic populations in Samburu County, Kenya. Consenting febrile patients were tested with RDTs and patient diagnosis and risk information were uploaded to a cloud database via the Deki Reader. Patients with positive diagnoses were provided digital vouchers for transportation to the clinic and treatment via their health wallet on their mobile phones. RESULTS: In total, 288 patients were tested during outreach visits, with 9% testing positive for brucellosis and 0.6% testing positive for malaria. All patients, regardless of diagnosis were provided with a mobile health wallet on their cellular phones to facilitate their transport to the clinic, and for patients testing positive for brucellosis or malaria, the wallet funded their treatment. The use of the Deki Reader in addition to quality diagnostics at point of care also facilitated geographic mapping of patient diagnoses in relation to key risk areas for brucellosis transmission. CONCLUSIONS: This study demonstrates that the Connected Dx approach can be effective even when addressing a remote, nomadic population and a rare disease, indicating that this approach to diagnosing, treatment, and payment for healthcare costs is feasible and can be scaled to address more prevalent diseases and conditions in more populous contexts.

Leishmania donovani infection drives the priming of human monocyte-derived dendritic cells during Plasmodium falciparum co-infections.

Functional impairment of dendritic cells (DCs) is part of a survival strategy evolved by Leishmania and Plasmodium parasites to evade host immune responses. Here, the effects of co-exposing human monocyte-derived DCs to Leishmania donovani promastigotes and Plasmodium falciparum-infected erythrocytes were investigated. Co-stimulation resulted in a dual, dose-dependent effect on DC differentiation which ranged from semi-mature cells, secreting low interleukin(-12p70 levels to a complete lack of phenotypic maturation in the presence of high parasite amounts. The effect was mainly triggered by the Leishmania parasites, as illustrated by their ability to induce semi-mature, interleukin-10-producing DCs, that poorly responded to lipopolysaccharide stimulation. Conversely, P. falciparum blood-stage forms failed to activate DCs and only slightly interfered with lipopolysaccharide effects. Stimulation with high L. donovani concentrations triggered phosphatidylserine translocation, whose onset presented after initiating the maturation impairment process. When added in combination, the two parasites could co-localize in the same DCs, confirming that the leading effects of Leishmania over Plasmodium may not be due to mutual exclusion. Altogether, these results suggest that in the presence of visceral leishmaniasis-malaria co-infections, Leishmania-driven effects may overrule the more silent response elicited by P. falciparum, shaping host immunity towards a regulatory pattern and possibly delaying disease resolution.

Decision-making on preimplantation genetic diagnosis and prenatal diagnosis: a challenge for couples with hereditary breast and ovarian cancer.

STUDY QUESTION: How do couples with a BRCA1/2 mutation decide on preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND) for hereditary breast and ovarian cancer syndrome (HBOC)? SUMMARY ANSWER: BRCA couples primarily classify PGD and/or PND as reproductive options based on the perceived severity of HBOC and moral considerations, and consequently weigh the few important advantages of PGD against numerous smaller disadvantages. WHAT IS KNOWN ALREADY: Awareness of PGD is generally low among persons at high risk for hereditary cancers. Most persons with HBOC are in favour of offering PGD for BRCA1/2 mutations, although only a minority would consider this option for themselves. Studies exploring the motivations for using or refraining from PGD among well-informed BRCA carriers of reproductive age are lacking. We studied the reproductive decision-making process by interviewing a group of well-informed, reproductive aged couples carrying a BRCA1/2 mutation, regarding their decisional motives and considerations. STUDY DESIGN, SIZE, DURATION: This exploratory, qualitative study investigated the motives and considerations taken into account by couples with a BRCA1/2 mutation and who have received extensive counselling on PGD and PND and have made a well-informed decision regarding this option. Eighteen couples took part in focus group and dyadic interviews between January and September 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Semi-structured focus groups were conducted containing two to four couples, assembled based on the reproductive method the couple had chosen: PGD (n = 6 couples) or conception without testing (n = 8 couples). Couples who had chosen PND for BRCA (n = 4) were interviewed dyadically. Two of the women, of whom one had chosen PND and the other had chosen no testing, had a history of breast cancer. MAIN RESULTS AND THE ROLE OF CHANCE: None of the couples who opted for PGD or conception without testing found the use of PND, with possible pregnancy termination, acceptable. PND users chose this method because of decisive, mainly practical reasons (natural conception, high chance of favourable outcome). Motives and considerations regarding PGD largely overlapped between PGD users, PND users and non-users, all mentioning some significant advantages (e.g. protecting the child and family from the mutation) and many smaller disadvantages (e.g. the necessity of in vitro fertilization (IVF), low chance of pregnancy by IVF/PGD). For female carriers, the safety of hormonal stimulation and the time required for PGD before undergoing preventive surgeries were important factors in the decision. Non-users expressed doubts about the moral justness of their decision afterwards and emphasized the impact the decision still had on their lives. LIMITATIONS, REASON FOR CAUTION: The interviewed couples were at different stages in their chosen trajectory, up to 3 years after completion. This may have led to recall bias of original motives and considerations. Couples who did not actively seek information about PGD were excluded. Therefore the results may not be readily generalizable to all BRCA couples. WIDER IMPLICATIONS OF THE FINDINGS: The perceived severity of HBOC and, for female carriers, the safety of hormonal stimulation and the time frames for PGD planning before preventive surgeries are essential items BRCA couples consider in reproductive decision-making. The emotional impact of this decision should not be underestimated; especially non-users may experience feelings of doubt or guilt up to several years afterwards. PGD counselling with tailored information addressing these items and decisional support in order to guarantee well-informed decision-making is needed. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Dutch breast cancer foundation Stichting Pink Ribbon, grant number 2010.PS11.C74. None of the authors have competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Old and new targets for innovative antimalarial compounds: the different strategies of the Italian Malaria Network.

Clinical treatment-failures to affordable drugs encouraged new investigation for discovery and development of new prophylactic and therapeutic interventions against malaria. The Drug Discovery Cluster (DDcl) of the Italian Malaria Network gathers several highly integrated and complementary laboratories from different Italian Institutions to identify, synthesise, screen in vitro and in vivo new antimalarial molecules directed against the intraerythrocytic stage of P. falciparum parasites and/or with transmission blocking activity to select lead compounds for further development. Complementary research activities, both in vitro and in the clinics, aim at investigating the pathogenetic mechanisms of severe malaria anaemia and the different manifestations of the disease in malaria-HIV co-infected patients to identify new therapies and improve survival.

In vitro evaluation of traditionally used Surinamese medicinal plants for their potential anti-leishmanial efficacy.

ETHNOPHARMACOLOGICAL RELEVANCE: Plant-based preparations are extensively used in Surinamese folk medicine for treating leishmaniasis, but often without a scientific rationale. AIM OF THE STUDY: To evaluate 25 Surinamese medicinal plants for their potential efficacy against leishmaniasis. MATERIALS AND METHODS: Concentrated plant extracts were evaluated for their effect on the viability of L. (V.) guyanensis AMC, L. (L.) major NADIM5, and L. (L.) donovani GEDII promastigotes, as well as intracellular amastigotes of L. (L.) donovani BHU814 in infected THP-1 cells. Selectivity was assessed by cytotoxicity against THP-1 cells. RESULTS: The only plant extract that showed potentially meaningful anti-leishmanial activity was that from Solanum lycocarpum that displayed mean IC50 values of about 51, 61, and <16 µg/mL against L. (V) guyanensis, L. (L) major, and L. (L) donovani promastigotes, respectively; about 374 µg/mL against L. (L) donovani amastigotes; and >500 µg/mL against THP-1 cells. The Bryophyllum pinnatum, Inga alba, and Quassia amara extracts displayed moderate to high IC50 values against promastigotes (about 51 to >500 µg/mL) and/or amastigotes (about 224 to >500 µg/mL) but were relatively toxic to THP-1 cells (IC50 values <16 to about 42 µg/mL). The remaining plant extracts exhibited in many cases IC50 values close to, around, or above 500µg/mL against promastigotes, amastigotes, and THP-1 cells. CONCLUSIONS: The S. lycocarpum preparation may be useful against leishmaniasis and may have a good safety index, warranting further investigations into its active constituents and mechanism(s) of action.