Visceral leishmaniasis in eastern Africa--current status.

Visceral leishmaniasis (VL) is among the most neglected of the tropical diseases, afflicting the poorest of the poor. In eastern Africa, VL causes at least 4000 deaths annually, a loss of approximately 385,000 disability-adjusted life years. Due to the chronicity of underlying causes, it is likely that the caseload will increase in the foreseeable future. While efforts should be pursued to develop novel case management and prevention tools, several effective interventions already exist but are rarely deployed. Funds are needed now to procure commodities and strengthen health systems, so that effective VL control can be delivered to populations at risk

Rapid Detection of Leishmania infantum Infection in Dogs: Comparative Study Using an Immunochromatographic Dipstick Test, Enzyme-Linked Immunosorbent Assay, and PCR

Current zoonotic visceral leishmaniasis (ZVL) control programs in Brazil include the culling of Leishmania infantum-infected reservoir dogs, a strategy that has failed to prevent a rise of canine and human ZVL cases over the past decade. One of the main reasons this strategy has failed is because of a long delay between sample collection, sample analysis, and control implementation. A rapid, sensitive, and specific diagnostic tool would be highly desirable, because it would allow control interventions to be implemented in situ. We compared an immunochromatographic dipstick test to enzyme-linked immunosorbent assay (ELISA) and PCR for detecting L. infantum infections in dogs from an area of ZVL endemicity in Brazil. The dipstick test was shown to have 61 to 75% specificity and 72 to 77% sensitivity, compared to 100% specificity for both ELISA and PCR and 71 to 88% and 51 to 64% sensitivity for ELISA and PCR, respectively. Of the field samples tested, 92 of 175 (53%), 65 of 175 (37%), and 47 of 175 (27%) were positive by dipstick, ELISA, and PCR, respectively. The positive and negative predictive values for the tested dipstick were 58 to 77% and 75%, respectively. Efforts should be made to develop a more specific dipstick test for diagnosis of leishmaniasis, because they may ultimately prove more cost-effective than currently used diagnostic tests when used in mass-screening surveys

Evaluation of PCR as a diagnostic mass-screening tool to detect Leishmania (Viannia) spp. in domestic dogs (Canis familiaris).

Several studies have suggested that the PCR could be used in epidemiological mass-screening surveys to detect Leishmania (Viannia) spp. infection in human and animal hosts. Dogs from an area of Leishmania braziliensis and Leishmania peruviana endemicity were screened for American cutaneous leishmaniasis (ACL) infection by established PCR-based and enzyme-linked immunosorbent antibody test (ELISA) protocols. PCR detected Leishmania (Viannia) infection in a total of 90 of 1,066 (8.4%) dogs: 32 of 368 (8.7%), 65 of 769 (8.5%), and 7 of 42 (16.7%) dogs were PCR positive by testing of whole blood, buffy coat, and bone marrow aspirates, respectively. ELISA detected infection in 221 of 1,059 (20.9%) tested dogs. The high prevalence of Leishmania (Viannia) detected by PCR and ELISA in both asymptomatic (7.5 and 19.2%, respectively) and symptomatic (32 and 62.5%, respectively) dogs is further circumstantial evidence for their suspected role as reservoir hosts of ACL. However, the low sensitivity of PCR (31%) compared to ELISA (81%) indicates that PCR cannot be used for mass screening of samples in ACL epidemiological studies. Unless more-sensitive PCR protocols were to be developed, its use should be restricted to the diagnosis of active (canine and human) cases and to the parasitological monitoring of patients after chemotherapy

Epidemiology and control of canine leishmaniasis in Peru and Brazil

The aims of the work presented in this thesis were two-fold: [i) to investigate whether domestic dogs are important reservoir hosts of ACL in a L. [Viannia]-endemic area where domestic transmission to humans has been reported [Part 1]; and [ii] to identify the shortcomings of currently practiced leishmaniasis dog control programmes and to evaluate whether topical insecticides could be used to control canine leishmaniasis [Part 2]. There is a growing belief that dogs [Canis familiaris] are peridomestic reservoirs of American cutaneous leishmaniasis [ACL] , as numerous studies have reported high ACL infection rates in dogs. The work described here is the first longitudinal study of ACL in dogs, and was carried out in 18 Leishmania [Viannia] -endemic villages of the Department of Huanuco, Peru. Over three years [1997-1999] a total 1104 dogs were surveyed, 104 of which prospectively. A polymerase chain reaction [PCR)] protocol to identify L. [Viannia] parasites in dogs was developed [Chapter 2], and, together with serology [ELISA. and IFAT], used to calculate prevalence and incidence of disease [Chapter 4]. The data was used to estimate the basic reproduction number [Ro] [Chapter 4] of canine ACL and to demonstrate a correlation between canine and human ACL incidences in the study villages [Chapter 5]. Several findings presented in Chapters 2-5 suggest that dogs are reservoir hosts of [peri-]domestic L. [Viannia] transmission in Huanuco, Peru. First, whereas the prevalence (3.8%) and incidence of clinical disease [4.2%] are low, the prevalence [25.6%] and incidence [29.0% per year] of L. [Viannia] infection in dogs is comparatively high. Second, the average duration of infection [2.2. years] can be as long as the mean life expectancy of an infected dog [2.5 years]. Third, L. [Viannia] parasites in dogs do not remain localised at the site of inoculation but are able to disseminate to both viscera and mucosa. Fourth, the detection of L. [Viannia] parasites by PCR in the blood of a high proportion of both symptomatic [32%] and asymptomatic [7.5%] dogs suggests that infected dogs are potentially infectious to sandfly vectors. Fifth, after controlling for inter-village differences in transmission rates, household dog ownership was shown to be a significant risk factor for human ACL. The results presented here show that if dogs were the main ACL reservoir host and if L. [Viannia] transmission were homogeneous, a dog control strategy (e.g. culling, insecticide-treated dog collars) in the study villages in Huanuco would be very feasible and effective, because the control effort [i.e. coverage] to reduce Ro<1 would be comparatively small [as low as 47%]. Domestic dogs are established reservoir hosts of ZVL caused by L. infantum. Hence, one of the approaches to reduce the incidence of human ZVL is to target infected dogs. The findings of a comparative study testing topical insecticides and applications to protect dogs from sandfly bites are presented in Chapter 7. It was shown that whilst permethrin and fenthion pour-on lotions had a more immediate effect on sandfly biting rates and mortality, deltamehtrin-impregnated collars [DMC] had a more prolonged protective effect, with the survival rate of bloodfed sandflies reduced by up to 86% after two months of deltamethrin collar application. In the work described in Chapter 8 the effectiveness of DMC to control canine ZVL was tested in a matched cluster intervention trial. Possible constraints associated with a community-wide implementation of a dog collar ZVL control strategy were also investigated using mathematical modelling. Although ZVL incidence was 32% lower in collared as compared to uncollared dogs after five months collar application, the difference was not significant. However, DMC did significantly reduce the odds (by 50%) of dogs increasing their anti-Leishmania antibody titre. Whether topical insecticides such as DMC will be effective as leishmaniasis control tools will depend on several factors. Firstly, the strategy will be most effective in those endemic areas where domestic dogs are the main ZVL reservoir and the epidemiological significance of wild reservoirs or stray dogs contributing to ZVL transmission is negligible. Secondly, in order to achieve a significant epidemiological impact on ZVL transmission, high dog collar coverage rates are essential. This will not only require the rapid replacement of lost collars, but also the collaring of new dogs recruited into the population; where population turnover rates are high, maintaining high coverage rates will be a greater logistic challenge, which invariably applies to dog populations in tropical, ZVL-endemic countries. Ultimately, the decision to replace the dog culling strategy with community-wide application of DMC will depend on [i] the relative cost of the interventions; and [ii] the practical applicability of DMC in the field [e.g. the willingness of the community to apply DMC and the efficiency with which they replace collars which have detached]. Clearly, the implementation of DMC on dogs is more likely to have the consent of the population at risk than the highly unpopular dog culling policy that continues to be practised in some ZVL-endemic countries.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Travel Is a Key Risk Factor for Malaria Transmission in Pre-Elimination Settings in Sub-Saharan Africa: A Review of the Literature and Meta-Analysis.

By sustaining transmission or causing malaria outbreaks, imported malaria undermines malaria elimination efforts. Few studies have examined the impact of travel on malaria epidemiology. We conducted a literature review and meta-analysis of studies investigating travel as a risk factor for malaria infection in sub-Saharan Africa using PubMed. We identified 22 studies and calculated a random-effects meta-analysis pooled odds ratio (OR) of 3.77 (95% CI: 2.49-5.70), indicating that travel is a significant risk factor for malaria infection. Odds ratios were particularly high in urban locations when travel was to rural areas, to more endemic/high transmission areas, and in young children. Although there was substantial heterogeneity in the magnitude of association across the studies, the pooled estimate and directional consistency support travel as an important risk factor for malaria infection

Leishmania (Viannia) spp. dissemination and tissue tropism in naturally infected dogs (Canis familiaris).

First evidence is presented for Leishmania (Viannia) spp. dissemination and tissue tropism in the domestic dog. Using PCR and histology, parasites were detected in the conjunctiva, lung, lymph nodes and ovaries of 2 naturally infected Peruvian dogs. The detection of parasites in the blood indicates that parasite dissemination to those organs may have been haematogenous