The Clinical Phenotypes of Cutaneous Leishmaniasis in Central and Southwest Regions of Yemen.

Background: Cutaneous leishmaniasis (CL) is endemic in Yemen. CL displays a spectrum of typical and atypical morphologies yet understudied in the central and southwest regions of Yemen. Aims and Objectives: To identify the typical and atypical clinical phenotypes of CL in the central and southwest regions of Yemen. Materials and Methods: A survey of 145 patients who visited Prof. Al-Qubati Clinic in Taiz between 2010 and 2015, was conducted. Results: Children and residents of the rural areas were at high risk of exposure to the insect vector. The typical phenotype was single (67%), facial (58%) and ulcerated nodule (35%). Other usual phenotypes were small ulcers (21.4%) and non-ulcerative papules and nodules (21%). Unusual phenotypes constituted 12% of the cohort and included psoriasiform, eczematous, erysipeloid, lupoid, verrucous, large ulcerative, leishmania recidivens, satellite, granulomatous infiltrative and hyperkeratotic plaques. Mucous membrane involvement was evident in 10.6% and was also polymorphic. Conclusion: CL has many morphologic patterns in central and southwest regions of Yemen, some are clinically deceptive.

Onchocerciasis (river blindness): larva-induced eczema (onchodermatitis) from an important oculocutaneous tropical disease spilling over into North America and Europe.

Onchocerciasis is a leading cause of blindness in the world. It may be seen in temperate climates of the United States and Europe in immigrants and travelers from endemic regions, often linked to poverty and war. One should be aware of an incubation period that can be up to 15 months. In its early stage and throughout its course, onchocerciasis has noteworthy skin findings, facilitating diagnosis, as onchodermatitis resembles common eczema with variable degrees of papular, lichenoid, atrophic, and pigmentary alterations, features not suggestive if one is unaware of an individual's immigration and travel history. The same concept applies for the encysted worms (onchocercomas), as they tend to appear as common skin cysts and benign neoplasms. New methods can be employed to increase diagnostic sensitivity and specificity. Ivermectin is the gold standard of therapy, the use of which has almost miraculously eliminated this disease from large areas of the earth. However, its effect remains isolated to microfilariae and can be devastating in those coinfected with Loa loa. Recently, the symbiotic relationship between adult worms and Wolbachia bacteria has been discovered and, with it, the possibility of adding doxycycline as a treatment option. We also discuss coinfection with HIV and other diseases.

A Serological Survey of Human Onchocerciasis in Yemen.

Yemen is a country that has been treating severe cases of oncho-dermatitis since 1992 and is now moving to a program aimed at the elimination of the transmission of Onchocerca volvulus. It is important to ensure that the currently acceptable tools used in epidemiological assessment of onchocerciasis in Africa and Latin America also apply to Yemen. Five hundred and ten blood samples from three known O. volvulus-endemic areas, locations that have never been under a mass treatment program, were tested for the presence of antibodies against a panel of O. volvulus-specific antigens using enzyme-linked immunosorbent assay (Ov16) and luciferase immunoprecipitation system (Ov-FAR-1 and Ov-MSA-1) assays. Overall, 31.4% of the samples tested were positive, with positivity increasing with age. Positivity was seen in 76.5% of those presenting with clinical onchocerciasis but importantly also in more than 28.5% of those defined as free of oncho-dermatitis; these latter individuals are likely to be serving as a source for persistent reinfection. This study supports the use of the current O. volvulus-specific serologic methodology in Yemen.

Onchocerciasis in Yemen: moving forward towards an elimination program.

The onchocerciasis focus in Yemen has been known for many years as an endemic area with unique characteristics, notably the atypical and most severe form of onchodermatitis, known as sowda or reactive onchodermatitis (ROD). The national effort to control the disease began in 1992 as an individual case treatment program by administering ivermectin to those presenting with ROD. The challenging geography of the endemic area and the current political and military unrest both underscore a need for special approaches when attempting to eliminate onchocerciasis from this country. An assessment of the national situation regarding this disease was carried out in 2011-2013 aimed at defining the best approach for moving from individual clinical case treatment to elimination of transmission. The history of the control efforts and the current status of the disease are reviewed and the essential changes needed to a mass drug administration (MDA) approach are identified as the national program addresses elimination. Yemen, despite the current troubles, has shown that it can successfully implement MDA programs despite many difficulties and therefore should be supported in its efforts towards countrywide elimination of this infection; however, success will need renewed national and international efforts.

Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae.

Leprosy is a chronic human disease caused by the yet-uncultured pathogen Mycobacterium leprae. Although readily curable with multidrug therapy (MDT), over 200,000 new cases are still reported annually. Here, we obtain M. leprae genome sequences from DNA extracted directly from patients' skin biopsies using a customized protocol. Comparative and phylogenetic analysis of 154 genomes from 25 countries provides insight into evolution and antimicrobial resistance, uncovering lineages and phylogeographic trends, with the most ancestral strains linked to the Far East. In addition to known MDT-resistance mutations, we detect other mutations associated with antibiotic resistance, and retrace a potential stepwise emergence of extensive drug resistance in the pre-MDT era. Some of the previously undescribed mutations occur in genes that are apparently subject to positive selection, and two of these (ribD, fadD9) are restricted to drug-resistant strains. Finally, nonsense mutations in the nth excision repair gene are associated with greater sequence diversity and drug resistance.

Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae

Leprosy is a chronic human disease caused by the yet-uncultured pathogen Mycobacterium leprae. Although readily curable with multidrug therapy (MDT), over 200,000 new cases are still reported annually. Here, we obtain M. leprae genome sequences from DNA extracted directly from patients' skin biopsies using a customized protocol. Comparative and phylogenetic analysis of 154 genomes from 25 countries provides insight into evolution and antimicrobial resistance, uncovering lineages and phylogeographic trends, with the most ancestral strains linked to the Far East. In addition to known MDT-resistance mutations, we detect other mutations associated with antibiotic resistance, and retrace a potential stepwise emergence of extensive drug resistance in the pre-MDT era. Some of the previously undescribed mutations occur in genes that are apparently subject to positive selection, and two of these (ribD, fadD9) are restricted to drug-resistant strains. Finally, nonsense mutations in the nth excision repair gene are associated with greater sequence diversity and drug resistance.

Cutaneous and mucocutaneous leishmaniasis: Clinical perspectives.

Leishmaniasis is endemic in 98 countries and territories, with 1.2 million new cases per year, making it a worldwide concern. The deadly visceral form is a leading cause of death from tropical parasitic infections, second only to malaria. Leishmaniasis appears to be increasing in many countries because of extended urbanization. The disease reservoir includes small mammals; parasite transmission occurs via bite of the female phlebotomine sandfly. Disease manifestations vary and largely depend upon the Leishmania species acquired. It may be first evident with a range of findings-from a localized cutaneous ulcer to diffuse painless dermal nodules-or, in the mucocutaneous form, ulceration of the oropharynx. In the potentially deadly visceral form, the internal organs and bone marrow are affected.

Cutaneous and mucocutaneous leishmaniasis: Differential diagnosis, diagnosis, histopathology, and management.

The diagnosis of leishmaniasis can be challenging because it mimics both infectious and malignant conditions. A misdiagnosis may lead to an unfavorable outcome. Using culture, histologic, and/or polymerase chain reaction study results, a diagnosis of leishmaniasis can be established and treatment initiated. Appropriate management requires an accurate diagnosis, which often includes identification of the specific etiologic species. Different endemic areas have varying sensitivities to the same medication, even within individual species. Species identification may be of practical value, because infections with select species have a substantial risk of visceral involvement. In addition, HIV and otherwise immunocompromised patients with leishmaniasis have a propensity for diffuse cutaneous leishmaniasis. For most New World Leishmania species, parenteral antimonial drugs remain the first line of therapy, while Old World species are easily treated with physical modalities. Historically, live organism vaccination has been used and is effective in preventing leishmaniasis, but results in an inoculation scar and an incubation period that may last for years. A more effective method of vaccination would be welcome.

Pyogenic granuloma of the lip - treatment with carbon dioxide slush cryosurgery as an approach in a resource-poor country.

Pyogenic granuloma (PG) is a benign vascular neoplasm most often evident as a rapidly developing solitary, sessile, or polypoid vascular nodule or tumor prone to ulceration or hemorrhage. Bleeding may be episodic, copious, and refractory to pressure, mandating treatment, particularly when on the lip. We describe a 14-year-old adolescent with a PG of the lower lip that responded to carbon dioxide slush cryosurgery, an option that may be of considerable value in a resource-poor country.

Cutaneous leishmaniasis: cryosurgery using carbon dioxide slush in a resource-poor country.

Leishmaniasis is a widespread parasitic disease seen most often in children and young adults, although it may occur at any age. In Yemen, up until now, specific treatment for cutaneous leishmaniasis (CL) has been challenging. Available chemotherapy is expensive and replete with significant side effects. Standard cryosurgery with liquid nitrogen is prohibitively expensive and often unavailable. The objective of this paper is to highlight the importance of cryosurgery with carbon dioxide slush in the treatment of CL in an economically underdeveloped region as a cost-effective, simple, successful, and affordable option.

Leprosy control in the Republic of Yemen: co-operation between government and non-government organizations, 1989-2003.

Although the prevalence rate of leprosy in the Republic of Yemen has dropped below the WHO elimination level of less than one case per 10,000 of the population, it is still regarded as a serious public health problem calling for continued vigilance, notably in the detection and treatment of hidden and undiagnosed cases. In the past, religious misinterpretation has generated adverse behaviour patterns towards people affected by leprosy, characterized by aggression, negligence and isolation. Until about 1982, following a visit of a leprologist (Dr S. K. Noordeen) from the World Health Organization, there was no leprosy control programme and attempts to establish one remained ineffective until in 1989, when an agreement was signed between the Ministry of Public Health and Population and the German Leprosy Relief Association. This led to the development of a leprosy control programme in four governorates, later extended to the rest of the country. This paper describes the progress made in the control of leprosy in the Yemen, 1989-2003, by the Ministry of Health and Population and the GLRA, in association with two local societies.

Review of leprosy control activities in Yemen

Leprosy control activities in Yemen are reviewed historically and up to the present time. Since 1983 the World Health Organization's multidrug therapy has been used in the National Leprosy Control Programme. Current activities are carried out in 63 leprosy clinics distributed all over the country and staffed by trained primary health care workers and medical assistants. In Yemen leprosy prevalence has declined from 1400 per 10,000 population in 1990 to 647 in 1997. Over the same period, new case detection rates per 10,000 population increased from 185 to 517. A backlog of leprosy cases continues to transmit the disease in Yemen.