The value of community participation in disease surveillance: a case study from Niger

A team of researchers, including one behavioral scientist (S.M.N.) and three epidemiologists (L.Q., O.S. and S.N.) conducted community analyses to assess the social and cultural factors that affect the detection and reporting of disease cases in a surveillance system, using acute flaccid paralysis (AFP) surveillance in Niger as a case study. Over a 60-day period in the country, the research team reviewed written field reports and interviewed epidemiologists, nurses, community members and persons in governmental and non-governmental organizations. Overall, we found that the logistical difficulties of travel and communication, which are common in developing countries, constrain the conventional surveillance system that relies on epidemiologists visiting sites to discover and investigate cases, particularly in rural areas. Other challenges include: community members' lack of knowledge about the possible link between a case of paralysis and a dangerous, communicable disease; lack of access to health care, including the low number of clinics and health care workers; cultural beliefs that favor seeking a local healer before consulting a nurse or physician; and health workers' lack of training in AFP surveillance. The quality of surveillance in developing countries can improve if a community-based approach is adopted. Such a system has been used successfully in Niger during smallpox-eradication and guinea worm-control campaigns. In a community-based system, community members receive basic education or more extensive training to motivate and enable them to notify health care staff about possible cases of disease in a timely fashion. Local organizations, local projects and local leaders must be included to ensure the success of such a program. In Niger we found sufficient quantities of this type of social capital, along with enough local experience of past health campaigns, to suggest that a community-based approach can improve the level of comprehensiveness and sensitivity of surveillance.     

Interactions of atropine with heterologously expressed and native alpha 3 subunit-containing nicotinic acetylcholine receptors

(1) Atropine, a classical muscarinic antagonist, has been reported previously to inhibit neuronal nicotinic acetylcholine receptors (nAChRs). In the present study, the action of atropine has been examined on alpha3beta4 receptors expressed heterologously in Xenopus oocytes and native nAChRs in medial habenula neurons. (2) At concentrations of atropine often used to inhibit muscarinic receptors (1 micro M), responses induced by near-maximal nicotine concentrations (100 micro M) at negative holding potentials (-65 mV) are inhibited (14-30%) in a reversible manner in both alpha4 and alpha3 subunit-containing heteromeric nAChRs. Half-maximal effective concentrations (IC(50) values) for atropine inhibition are similar for the four classes of heteromeric receptors studied (4-13 micro M). (3) For alpha3beta4 nAChRs in oocytes, inhibition by atropine (10 micro M) is not overcome at higher concentrations of agonist, and is increased with membrane hyperpolarization. These results are consistent with non-competitive antagonism--possibly ion channel block. (4) At low concentrations of both nicotine (10 micro M) and atropine (<10 micro M), potentiation ( approximately 25%) of alpha3beta4 nAChR responses in oocytes is observed. The relative balance between potentiation and inhibition is dependent upon membrane potential. (5) In rat medial habenula (MHb) neurons, atropine (0.3-3.0 micro M) inhibited nicotine-induced responses in both a concentration and membrane potential-dependent manner (at -40 mV, IC(50)=4 micro M), similar to the effects on alpha3beta4-nAChRs in oocytes. However, unlike heterologously expressed receptors, potentiation was barely detectable at depolarized membrane potentials using low concentrations of nicotine (3-10 micro M). Conversely, the weak agonist, choline (1-3 mM) was observed to augment responses of MHb nAChRs.     

Substrates and temperature differentiate ion flux from serotonin flux in a serotonin transporter

Neurotransmitter transporters couple the transport of transmitter against its concentration gradient to the electrochemical potential of associated ions which are also transported. Recent studies of some neurotransmitter transporters show them to have properties of both traditional carriers and substrate-dependent ion channels, in that ion fluxes are in excess of that predicted from stoichiometric substrate fluxes. Whether these properties are comparable for all transporters, the extent to which these permeation states are independent, and whether the relationship between these two states can be regulated are not well understood. To address these questions, we expressed the Drosophila serotonin (5HT) transporter (dSERT) in Xenopus oocytes and measured both substrate-elicited ion flux and 5HT flux at various temperatures and substrate concentrations. We find that the ion flux and 5HT flux components of the transport process have a significant temperature dependence suggesting that ion flux and transmitter flux arise from a similar thermodynamically-coupled process involving large conformational changes (e.g., gating). These data are in contrast to those shown for glutamate transporters, suggesting a different permeation process for 5HT transporters. The relationship between ion flux and 5HT flux is differentially regulated by chloride and 5HT, suggesting that these permeation states are distinct. The difference in half-maximal 5HT concentration necessary to mediate ion flux and 5HT flux occurs at submicromolar 5HT concentrations suggesting that the relative participation of dSERT in ion flux and 5HT flux will be determined by the synaptic 5HT concentration.     

Superoxide stress identifies neurons at risk in a model of ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder caused by mutations in the ATM gene. A-T children demonstrate sensitivity to ionizing radiation, predisposition to hematological malignancies, and telangiectasias. However, the hallmark of A-T is fulminant degeneration of cerebellar Purkinje cells accompanied by a progressive ataxia with features of both cerebellar and basal ganglia dysfunction. Although the ATM gene product (ATM) is known to be involved in DNA repair, the mechanisms that link loss of ATM with neurodegeneration remain unknown. Recently, it has been suggested that abnormalities in redox status contribute to the A-T phenotype. To address this question in the nervous system, we measured reactive oxygen species (ROS) in brain regions and specific neuronal populations in ATM-/- mice. We found increased ROS levels in cerebellum and striatum but not cortex of ATM-/- mice compared to ATM+/+ mice. Confocal microscopic examination revealed elevated superoxide levels in cerebellar Purkinje cells and nigral dopaminergic neurons but not cortical neurons, thus mapping increased superoxide levels onto the neuronal populations selectively affected in A-T. These data are the first demonstration of elevated levels of ROS in neurons at risk in any genetic neurodegenerative disorder and, furthermore, suggest that ATM acts as a pro-survival signal in post-mitotic Purkinje cells and dopaminergic neurons by modifying superoxide radical handling in these selectively vulnerable neurons.     

Challenges in implementing a point-of-use water quality intervention in rural Kenya

To prevent diarrheal diseases in western Kenya, CARE Kenya initiated the Water, Sanitation, and Education for Health (WASEH) Project in 1998. The project targets 72 farming and fishing communities with a total population of 43 000. Although the WASEH Project facilitated construction of shallow wells and pit latrines, the water quality still needed improvement. Consequently, in 2001, CARE implemented the Safe Water System (which consists of point-of-use water treatment with sodium hypochlorite, safe storage, and behavior change techniques) within the already established WASEH infrastructure, using existing community organizations in combination with a social marketing approach that introduced affordable products. The project has resulted in adoption rates of 33.5% for chemical water treatment and 18.5% for clay pots modified for safe water storage.     

Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A

Plasma membrane GABA transporters participate in neural signaling through re-uptake of neurotransmitter. The domains of the transporter that mediate GABA translocation and regulate transport are not well understood. In the present experiments, the N-terminal cytoplasmic domain of the GABA transporter GAT1 regulated substrate transport rates. This domain directly interacted with syntaxin 1A, a SNARE protein involved in both neurotransmitter release and modulation of calcium channels and cystic fibrosis transmembrane regulator (CFTR) chloride channels. The interaction resulted in a decrease in transporter transport rates. These data demonstrate that intracellular domains of the GABA and protein-protein interactions regulate substrate translocation, and identify a direct link between the machinery involved in transmitter release and re-uptake.