Vaccines for Visceral Leishmaniasis: Hopes and Hurdles

The leishmaniases are vector-borne parasitic diseases with multiple disease phenotypes that range from self-healing cutaneous ulcers to disfiguring post-kala-azar dermal leishmaniasis and fatal visceral leishmaniasis (VL). Infected individuals can develop subclinical infections or overt disease. Current treatments are toxic and expensive. The only successful control measure is case detection and drug treatment. Resistance to anti-leishmanial drugs are increasing with few drugs in the pipeline. The Leishmania parasites are good candidates for vaccine development, with no change in its antigenic coat and extensive cross-reactivity between species. First-generation vaccines are safe, immunogenic with inconclusive efficiency. These vaccines presented the leishmanin skin test (LST) as a potentially good surrogate marker of immunogenicity/protection that can help in future vaccine studies. First-generation vaccines are the only leishmaniasis vaccines that progressed to phase III. Second-generation vaccines are safe and immunogenic, but none progressed to phase III. Third-generation vaccines recently entered human testing. Alternative approaches include in silico prediction of immunogenic Leishmania epitopes with in vitro immunogenicity testing. New adjuvants can help in the quest to develop efficacious leishmaniasis vaccines. Failure of second- and third-generation vaccines to reach phase III, rising drug resistance and continued VL pandemics make it a necessity to revisit first-generation vaccines

Diagnostic predictive values of the hain genotype MTBDRsl assay in mycobacterial strains isolated from Sudan

Introduction: hain GenoType MTBDRsl is nucleic acid amplification assay based on reverse hybridization with specific oligonucleotide probes on nitrocellulose strips. MTBDRsl identifies M. tuberculosis complex and detects resistance to fluoroquinolone, second line injectable drugs and ethambutol evident as mutations of gyrA, rrs and embB genes respectively. This study aimed to evaluate the diagnostic performance of the Hain GenoType MTBDRsl Assay using 1% proportion method on LJ medium as gold standard. Methods: a total of 52 rifampicin resistant (RR) isolates were tested for second line drug sensitivity by 1% proportion method and by MTBDRsl assay. Results: two strains were identified as mycobacteria other than tuberculosis MOTT and the rest were Mycobacterium tuberculosis complex MTBC. Five of the MTBC isolates (5/50; 10%) showed resistance to at least one second line drug and one isolate (1/50; 2%) was XDR. XDR strain was concordantly detected by the two methods. One of two Kanamycin-resistant isolates showed discordant result. Ofloxacin showed one false positive and one false negative result. Most discrepancies were detected with Ethambutol. The sensitivity, specificity, positive and negative predictive values were respectively as follows: Ethambutol (63.3.4%, 85.7%, 94.4% and 62%): for Kanamycin (67%, 100%, 100% and 97.9%): for Amikacin and Capreomycin (100%, 100%, 100% and 100%): for Ofloxacin (75%, 97.5%, 75% and 97.8%). For XDR isolate the values were (100%, 100%, 100% and 100%) respectively. Conclusion: MTBDRsl showed high specificity and negative predictive values making it acceptable and time-saving for early presumptive detection of resistance to second-line drugs in Sudan

Bone Marrow and Peripheral Blood Cells Toxicity of a Single 2.0 Gy Cobalt60 Ionizing Radiation: An Animal Model

BACKGROUND: Bone marrow is extremely vulnerable to damage caused by radiation therapy. Hence, bone marrow suppression is an important side effect of radiotherapy. Effective use of radiotherapy is therefore compromised by radiation-related injuries.MATERIAL AND METHODS: Six Guinea-pigs were recruited for the study of which three were subjected to total body irradiation with Co60 while the other three served as controls. Bone marrow and peripheral blood samples were collected before and at days 9, 14 and 21, post irradiation. Manual and automated counts were performed for bone marrow nucleated cells and peripheral blood cells respectively.RESULTS: Declining bone marrow cellularity was evident immediately post irradiation. Mean ± SD of marrow cell counted per mm3 were 121,924±281, 87,603±772, 121,367±375 and122,750±1000 pre-irradiation and days 9, 14 and 21, postirradiation (p-values 0.10, 0.27 and 0.29 respectively). Significant drops in counts were noticed on day 9 post-irradiation for all red cell parameters (p-values <0.05), for Total White Blood Cell Count and Neutrophil count (p-values <0.05) and also on days 14 and 21 for Lymphocytes (p-values <0.05) and on day 21 for Eosinophil/Basophil/Monocytes (p-value <0.05). A significant drop in platelets counts was also noticed on day 9 (p-value <0.05) which significantly increased above pre-irradiation value on day 21.CONCLUSION: Total body irrradiation with Co60 significantly affects the bone marrow with maximum reductions in marrow nucleated cells and peripheral blood cells counts on day 9 post irradiation.

Post-Kala-Azar Dermal Leishmaniasis: A Paradigm of Paradoxical Immune Reconstitution Syndrome in Non-HIV/AIDS Patients

Visceral leishmaniasis (VL) is a parasitic disease characterized by immune suppression. Successful treatment is usually followed by immune reconstitution and a dermatosis called post-Kala-azar dermal leishmaniasis (PKDL). Recently, PKDL was described as one of the immune reconstitution syndromes (IRISs) in HIV/VL patients on HAART. This study aimed to present PKDL as a typical example of paradoxical IRIS in non-HIV/AIDS individuals. Published and new data on the pathogenesis and healing of PKDL was reviewed and presented. The data suggested that PKDL is a typical example of paradoxical IRIS, being a new disease entity that follows VL successful treatment and immune recovery. PKDL lesions are immune inflammatory in nature with granuloma, adequate response to immunochemotherapy, and an ensuing hypersensitivity reaction, the leishmanin skin test (LST). The data also suggested that the cytokine patterns of PKDL pathogenesis and healing are probably as follows: an active disease state dominated by IL-10 followed by spontaneous/treatment-induced IL-12 priming, IL-2 stimulation, and INF-γ production. INF-γ-activated macrophages eliminate the Leishmania parasites/antigen to be followed by LST conversion and healing. In conclusion, PKDL is a typical example of paradoxical IRIS in non-HIV/AIDS individuals with anti-inflammatory cytokine patterns that are superseded by treatment-induced proinflammatory cytokines and lesions healing

Peer Reproductive Health Education Trial in Eritrea

Reproductive health is a state of physical, mental and social well-being in all matters relating to the reproductive system at all stages of life. In East Africa including Eritrea, adolescents comprise more than a quarter of the population

The Effect of Peer Education on Peer Educators

Peer reproductive health education has been in use in developed and developing countries and its efficacy in changing knowledge and attitude of education beneficiaries is reported. On the other hand despite its wide use, reports on its effect on peer educators are scarce

Cure of post Kala-azar dermal leishmaniasis with paromomycin/sodium stibogluconate combination: a proof of concept

Background: Post kala-azar dermal leishmaniasis (PKDL) is  a  recognized  dermatologic  complication  of  successfully  treated  visceral  leishmaniasis  (VL). PKDL lesions are suspected to be important reservoirs for VL transmission in Sudan. Prolonged treatment schedules, feeling of general well-being and the social stigmata of PKDL prevent most patients seeking treatment. The mainstay of treatment is cardiotoxic sodium stibogluconate (SSG) for 60-120 days. Recently, liposomal amphotericin B (Ambisome®) and immunochemotherapy gave promising results. Ambisome® is expensive and difficult to prepare under field conditions. Paromomycin/SSG combination has been shown to be safe, efficacious and can save time in VL treatment. This study aims to prove that Paromomycin/SSG combination can cure and reduce PKDL treatment duration.Methods:We are reporting nine cases of patients with PKDL lesions of ≥6 months duration who were diagnosed by clinical signs, histopathological/immunohistochemical and PCR.Results: Patients’ mean age was 11.7 ± 4.3 years. A third of the patients (3/9; 33.3%) who failed previous SSG treatment of 2-3 months duration responded completely to 40 days of paromomycin/SSG combination. The majority of patients (5/9; 55.6%) responded completely to 30 days of the combination. One patient (1/9; 11.1%) relapsed following 30 days paromomycin/SSG combination.Conclusion:It was concluded that paromomycin/SSG combination for 30 days is time-saving, safe and efficacious for PKDL treatment.

Burden of Reproductive Health Illiteracy in Eritrea

Reproductive health (RH) is state of physical, mental, and social well-being in all matters relating to the reproductive system, at all stages of life. In East Africa including Eritrea, adolescents comprise more than a quarter of the population. The region holds the highest rates of sexually transmitted diseases, HIV, unwanted pregnancy and unsafe abortion with its complications. Young girls carry the highest burden of reproductive health problems due to their risk taking behavior, lack of knowledge, peer pressure, physiologic immaturity and low socioeconomic status. The purpose of this study is to assess the burden of reproductive health illiteracy on adolescent high school girls in Eritrea

Paromomycin for the Treatment of Visceral Leishmaniasis in Sudan: A Randomized, Open-Label, Dose-Finding Study

Visceral leishmaniasis (VL) is a parasitic disease transmitted through the bite of sandflies. The WHO estimates 500,000 new cases of VL each year, with more than 90% of cases occurring in Southeast Asia, East Africa, and South America. If left untreated, VL can be fatal. We had previously conducted a large multi-center study in Sudan, East Africa, to assess the efficacy of paromomycin (PM) alone or in combination with sodium stibogluconate. Clinical studies in India have shown that 15 mg/kg/day PM for 21 days was an effective cure. However, the same treatment regimen was not efficacious in two study sites in Sudan. Here, our aim was to assess two high-dose regimens of PM in Sudan: 15 mg/kg/day for 28 days and 20 mg/kg/day for 21 days. The results suggest that, at these total doses, PM is more efficacious than when given daily at 15 mg/kg for 21 days, and that high doses are required to treat VL in Sudan. Efficacy of 20 mg/kg/day PM for 21 days is currently being evaluated in a prospective, comparative phase III trial in East Africa