Interventions for Old World cutaneous leishmaniasis.

BACKGROUND: Cutaneous leishmaniasis, caused by a parasitic infection, is considered one of the most serious skin diseases in many low- and middle-income countries. Old World cutaneous leishmaniasis (OWCL) is caused by species found in Africa, Asia, the Middle East, the Mediterranean, and India. The most commonly prescribed treatments are antimonials, but other drugs have been used with varying success. As OWCL tends to heal spontaneously, it is necessary to justify the use of systemic and topical treatments. This is an update of a Cochrane Review first published in 2008. OBJECTIVES: To assess the effects of therapeutic interventions for the localised form of Old World cutaneous leishmaniasis. SEARCH METHODS: We updated our searches of the following databases to November 2016: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). We wrote to national programme managers, general co-ordinators, directors, clinicians, WHO-EMRO regional officers of endemic countries, pharmaceutical companies, tropical medicine centres, and authors of relevant papers for further information about relevant unpublished and ongoing trials. We undertook a separate search for adverse effects of interventions for Old World cutaneous leishmaniasis in September 2015 using MEDLINE. SELECTION CRITERIA: Randomised controlled trials of either single or combination treatments in immunocompetent people with OWCL confirmed by smear, histology, culture, or polymerase chain reaction. The comparators were either no treatment, placebo/vehicle, and/or another active compound. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias and extracted data. We only synthesised data when we were able to identify at least two studies investigating similar treatments and reporting data amenable to pooling. We also recorded data about adverse effects from the corresponding search. MAIN RESULTS: We included 89 studies (of which 40 were new to this update) in 10,583 people with OWCL. The studies included were conducted mainly in the Far or Middle East at regional hospitals, local healthcare clinics, and skin disease research centres. Women accounted for 41.5% of the participants (range: 23% to 80%). The overall mean age of participants was 25 years (range 12 to 56). Most studies lasted between two to six months, with the longest lasting two years; average duration was four months. Most studies were at unclear or high risk for most bias domains. A lack of blinding and reporting bias were present in almost 40% of studies. Two trials were at low risk of bias for all domains. Trials reported the causative species poorly.Here we provide results for the two main comparisons identified: itraconazole (200 mg for six to eight weeks) versus placebo; and paromomycin ointment (15% plus 10% urea, twice daily for 14 days) versus vehicle.In the comparison of oral itraconazole versus placebo, at 2.5 months' follow up, 85/125 participants in the itraconazole group achieved complete cure compared to 54/119 in the placebo group (RR 3.70, 95% CI 0.35 to 38.99; 3 studies; 244 participants). In one study, microbiological or histopathological cure of skin lesions only occurred in the itraconazole group after a mean follow-up of 2.5 months (RR 17.00, 95% CI 0.47 to 612.21; 20 participants). However, although the analyses favour oral itraconazole for these outcomes, we cannot be confident in the results due to the very low certainty evidence. More side effects of mild abdominal pain and nausea (RR 2.36, 95% CI 0.74 to 7.47; 3 studies; 204 participants) and mild abnormal liver function (RR 3.08, 95% CI 0.53 to 17.98; 3 studies; 84 participants) occurred in the itraconazole group (as well as reports of headaches and dizziness), compared with the placebo group, but again we rated the certainty of evidence as very low so are unsure of the results.When comparing paromomycin with vehicle, there was no difference in the number of participants who achieved complete cure (RR of 1.00, 95% CI 0.86, 1.17; 383 participants, 2 studies) and microbiological or histopathological cure of skin lesions after a mean follow-up of 2.5 months (RR 1.03, CI 0.88 to 1.20; 383 participants, 2 studies), but the paromomycin group had more skin/local reactions (such as inflammation, vesiculation, pain, redness, or itch) (RR 1.42, 95% CI 0.67 to 3.01; 4 studies; 713 participants). For all of these outcomes, the certainty of evidence was very low, meaning we are unsure about these results.Trial authors did not report the percentage of lesions cured after the end of treatment or speed of healing for either of these key comparisons. AUTHORS' CONCLUSIONS: There was very low-certainty evidence to support the effectiveness of itraconazole and paromomycin ointment for OWCL in terms of cure (i.e. microbiological or histopathological cure and percentage of participants completely cured). Both of these interventions incited more adverse effects, which were mild in nature, than their comparisons, but we could draw no conclusions regarding safety due to the very low certainty of the evidence for this outcome.We downgraded the key outcomes in these two comparisons due to high risk of bias, inconsistency between the results, and imprecision. There is a need for large, well-designed international studies that evaluate long-term effects of current therapies and enable a reliable conclusion about treatments. Future trials should specify the species of leishmaniasis; trials on types caused by Leishmania infantum, L aethiopica, andL donovani are lacking. Research into the effects of treating women of childbearing age, children, people with comorbid conditions, and those who are immunocompromised would also be helpful.It was difficult to evaluate the overall efficacy of any of the numerous treatments due to the variable treatment regimens examined and because RCTs evaluated different Leishmania species and took place in different geographical areas. Some outcomes we looked for but did not find were degree of functional and aesthetic impairment, change in ability to detect Leishmania, quality of life, and emergence of resistance. There were only limited data on prevention of scarring.

Interventions for Old World cutaneous leishmaniasis.

BACKGROUND: Cutaneous leishmaniasis, caused by a parasitic infection, is considered one of the most serious skin diseases in many low- and middle-income countries. Old World cutaneous leishmaniasis (OWCL) is caused by species found in Africa, Asia, the Middle East, the Mediterranean, and India. The most commonly prescribed treatments are antimonials, but other drugs have been used with varying success. As OWCL tends to heal spontaneously, it is necessary to justify the use of systemic and topical treatments. This is an update of a Cochrane Review first published in 2008. OBJECTIVES: To assess the effects of therapeutic interventions for the localised form of Old World cutaneous leishmaniasis. SEARCH METHODS: We updated our searches of the following databases to November 2016: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). We wrote to national programme managers, general co-ordinators, directors, clinicians, WHO-EMRO regional officers of endemic countries, pharmaceutical companies, tropical medicine centres, and authors of relevant papers for further information about relevant unpublished and ongoing trials. We undertook a separate search for adverse effects of interventions for Old World cutaneous leishmaniasis in September 2015 using MEDLINE. SELECTION CRITERIA: Randomised controlled trials of either single or combination treatments in immunocompetent people with OWCL confirmed by smear, histology, culture, or polymerase chain reaction. The comparators were either no treatment, placebo/vehicle, and/or another active compound. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias and extracted data. We only synthesised data when we were able to identify at least two studies investigating similar treatments and reporting data amenable to pooling. We also recorded data about adverse effects from the corresponding search. MAIN RESULTS: We included 89 studies (of which 40 were new to this update) in 10,583 people with OWCL. The studies included were conducted mainly in the Far or Middle East at regional hospitals, local healthcare clinics, and skin disease research centres. Women accounted for 41.5% of the participants (range: 23% to 80%). The overall mean age of participants was 25 years (range 12 to 56). Most studies lasted between two to six months, with the longest lasting two years; average duration was four months. Most studies were at unclear or high risk for most bias domains. A lack of blinding and reporting bias were present in almost 40% of studies. Two trials were at low risk of bias for all domains. Trials reported the causative species poorly.Here we provide results for the two main comparisons identified: itraconazole (200 mg for six to eight weeks) versus placebo; and paromomycin ointment (15% plus 10% urea, twice daily for 14 days) versus vehicle.In the comparison of oral itraconazole versus placebo, at 2.5 months' follow up, 85/125 participants in the itraconazole group achieved complete cure compared to 54/119 in the placebo group (RR 3.70, 95% CI 0.35 to 38.99; 3 studies; 244 participants). In one study, microbiological or histopathological cure of skin lesions only occurred in the itraconazole group after a mean follow-up of 2.5 months (RR 17.00, 95% CI 0.47 to 612.21; 20 participants). However, although the analyses favour oral itraconazole for these outcomes, we cannot be confident in the results due to the very low certainty evidence. More side effects of mild abdominal pain and nausea (RR 2.36, 95% CI 0.74 to 7.47; 3 studies; 204 participants) and mild abnormal liver function (RR 3.08, 95% CI 0.53 to 17.98; 3 studies; 84 participants) occurred in the itraconazole group (as well as reports of headaches and dizziness), compared with the placebo group, but again we rated the certainty of evidence as very low so are unsure of the results.When comparing paromomycin with vehicle, there was no difference in the number of participants who achieved complete cure (RR of 1.00, 95% CI 0.86, 1.17; 383 participants, 2 studies) and microbiological or histopathological cure of skin lesions after a mean follow-up of 2.5 months (RR 1.03, CI 0.88 to 1.20; 383 participants, 2 studies), but the paromomycin group had more skin/local reactions (such as inflammation, vesiculation, pain, redness, or itch) (RR 1.42, 95% CI 0.67 to 3.01; 4 studies; 713 participants). For all of these outcomes, the certainty of evidence was very low, meaning we are unsure about these results.Trial authors did not report the percentage of lesions cured after the end of treatment or speed of healing for either of these key comparisons. AUTHORS' CONCLUSIONS: There was very low-certainty evidence to support the effectiveness of itraconazole and paromomycin ointment for OWCL in terms of cure (i.e. microbiological or histopathological cure and percentage of participants completely cured). Both of these interventions incited more adverse effects, which were mild in nature, than their comparisons, but we could draw no conclusions regarding safety due to the very low certainty of the evidence for this outcome.We downgraded the key outcomes in these two comparisons due to high risk of bias, inconsistency between the results, and imprecision. There is a need for large, well-designed international studies that evaluate long-term effects of current therapies and enable a reliable conclusion about treatments. Future trials should specify the species of leishmaniasis; trials on types caused by Leishmania infantum, L aethiopica, andL donovani are lacking. Research into the effects of treating women of childbearing age, children, people with comorbid conditions, and those who are immunocompromised would also be helpful.It was difficult to evaluate the overall efficacy of any of the numerous treatments due to the variable treatment regimens examined and because RCTs evaluated different Leishmania species and took place in different geographical areas. Some outcomes we looked for but did not find were degree of functional and aesthetic impairment, change in ability to detect Leishmania, quality of life, and emergence of resistance. There were only limited data on prevention of scarring.

Spatial clustering and risk factors of malaria infections in Bata district, Equatorial Guinea.

BACKGROUND: The transmission of malaria is intense in the majority of the countries of sub-Saharan Africa, particularly in those that are located along the Equatorial strip. The present study aimed to describe the current distribution of malaria prevalence among children and its environment-related factors as well as to detect malaria spatial clusters in the district of Bata, in Equatorial Guinea. METHODS: From June to August 2013 a representative cross-sectional survey using a multistage, stratified, cluster-selected sample was carried out of children in urban and rural areas of Bata District. All children were tested for malaria using rapid diagnostic tests (RDTs). Results were linked to each household by global position system data. Two cluster analysis methods were used: hot spot analysis using the Getis-Ord Gi statistic, and the SaTScan™ spatial statistic estimates, based on the assumption of a Poisson distribution to detect spatial clusters. In addition, univariate associations and Poisson regression model were used to explore the association between malaria prevalence at household level with different environmental factors. RESULTS: A total of 1416 children aged 2 months to 15 years living in 417 households were included in this study. Malaria prevalence by RDTs was 47.53%, being highest in the age group 6-15 years (63.24%, p < 0.001). Those children living in rural areas were there malaria risk is greater (65.81%) (p < 0.001). Malaria prevalence was higher in those houses located <1 km from a river and <3 km to a forest (IRR: 1.31; 95% CI 1.13-1.51 and IRR: 1.44; 95% CI 1.25-1.66, respectively). Poisson regression analysis also showed a decrease in malaria prevalence with altitude (IRR: 0.73; 95% CI 0.62-0.86). A significant cluster inland of the district, in rural areas has been found. CONCLUSIONS: This study reveals a high prevalence of RDT-based malaria among children in Bata district. Those households situated in inland rural areas, near to a river, a green area and/or at low altitude were a risk factor for malaria. Spatial tools can help policy makers to promote new recommendations for malaria control.

Detección de la infección por el VIH en los servicios de urgencias españoles: ¿realidad o utopía? / Detection of human immunodeficiency virus infection in Spanish emergency departments: reality or to utopian dream?

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Travelers' Diarrhea in Children at Risk: An Observational Study From a Spanish Database.

BACKGROUND: Gastrointestinal symptoms are a common cause of consultation about children traveling to or coming from developing countries. The aim of this study was to identify the risk factors associated with gastrointestinal syndrome in children who travel. METHODS: A prospective observational analytical and multicenter study was performed within +Redivi, a Spanish Tropical Medicine network on imported infections, from January 2009 to December 2013. All participants aged 16 years and younger were included in the analysis. Ethical approval was obtained from all the participating centers. RESULTS: A total of 606 children ≤16 years of age were registered in the +Redivi database during the study period. Median age was 8.7 years (interquartile range, 4.4-12.4 years), 65.8% (399/606) were immigrants, 90% were >2 years old and 54% were male. Median travel duration, excluding immigrants, was 50 days (interquartile range, 30-150 days). Children with gastrointestinal symptoms represented 13.5% (82/606) of total consultations. A significant association was found in bivariate analysis between gastrointestinal disorder and age <2 years (P < 0.01) and travel duration (P = 0.046). Immigrants had less gastrointestinal disorders than tourists (P < 0.05). The most prevalent infection was protozoan in 23.4% (142/606), and Giardia intestinalis was the most common pathogen in 10.1% (61/606) of total children. Independent risk factors for gastrointestinal symptoms were tourist and traveler child visiting friends and relatives (P = 0.03), travel duration <90 days (P = 0.008) and bacterial cause (P < 0.001). CONCLUSIONS: Traveling children who developed a gastrointestinal syndrome represented 13.5% of the total pediatric consultations in +Redivi. Independent risk factors were tourist or traveler visiting friends and relatives, travel duration <90 days and bacterial infection. G. intestinalis was the most common infectious agent causing a gastrointestinal disorder in the traveler children.

Malaria prevalence in Bata district, Equatorial Guinea: a cross-sectional study.

BACKGROUND: Malaria has traditionally been a leading public health problem in Equatorial Guinea. After completion, in September 2011, of the integrated set of interventions against malaria launched by the Global Fund Malaria Programme in the mainland area, the epidemiological situation of malaria remains unknown. The aim of this study was to investigate the prevalence rate of malaria and associated factors based on the rapid diagnosis test (RDT) in Bata district, in order to provide evidence that will reinforce the National Malaria Control Programme. METHODS: From June to August 2013, a representative cross sectional survey using a multistage, stratified, cluster-selected sample was carried out in urban zones and rural villages from Bata district. Data on socio-demographic, health status and malaria-related behaviours was collected. Malaria diagnosis was performed by RDT. Bivariate and multivariable statistical methods were employed to assess malaria prevalence and its association with different factors. RESULTS: Prevalence of malaria was higher in rural settings (58.9 %; CI 95 % 55.2-62.5 %) than in the sampled urban communities (33.9 %; CI 95 % 31.1-36.9 %). Presence of anaemia was also high, especially in rural sites (89.6 vs. 82.8 %, p < 0.001). The analyses show that a positive RDT result was significantly associated with age group, the most affected age range being 13 months-14 years old. Other significant covariates were ethnic group (only in urban sites), number of adults living in the house (only in rural villages) previous history of fever, anaemia (only in urban sites) and sleeping under a bed net. Moreover, those who never slept under a bed net were two times more likely to have malaria. CONCLUSION: The prevalence of malaria was high in Bata district, especially in rural villages. The National Programme to fight malaria in Equatorial Guinea should take into account the differences found between rural and urban communities and age groups to target appropriately those worst affected. The findings of this study will assist in planning and undertaking regional policy and other preventive initiatives.