Niaz Muhammad

Interferon-Gamma Improves Macrophages Function against M. tuberculosis in Multidrug-Resistant Tuberculosis Patients

Background. Mycobacterium tuberculosis (M. tuberculosis) that causes tuberculosis (TB) kills millions of infected people annually especially multidrug-resistant tuberculosis (MDR-TB). On infection, macrophages recognize the mycobacteria by toll-like receptor (TLR) followed by phagocytosis and control of mycobacteria. In addition, macrophages also secrete IL-12 to induce IFN-γ production by T, which, in turn, increases the phagocytosis and oxidative burst. Individuals with defects in innate or adaptive immunity exhibit increased susceptibility to M. tuberculosis. Understanding these immunologic mechanisms will help in TB control. We aimed to investigate the immunopathologic mechanisms in MDR-TB and role of recombinant human interferon-gamma (rhIFN-γ). Study Design and Methods. Monocyte-derived macrophages (MDMs) were generated from peripheral blood mononuclear cells of MDR-TB patients and healthy subjects and were investigated for immunologic response by ELISA and flow cytometry. Results. Different functional and molecular anomalies were observed in macrophages. In addition, a defective immune response to M. tuberculosis from the patients MDMs was characterized, which in turn improved by pretreatment with rhIFN-γ. Conclusion. This work highlights the fact that rhIFN-γ improves macrophages function against M. tuberculosis and treatment of patients with poor responsiveness to TB therapy may be needed in future to include IFN-γ as adjuvant therapy after the full characterization of pathological and molecular mechanisms in these and in other more multidrug-resistant TB patients.

A Homozygous Missense Mutation in SLC25A16 is Associated with Autosomal Recessive Isolated Fingernail Dysplasia in a Pakistani Family

Developmental nail disorders are heterogeneous group of genodermatosis, with nonsyndromic congenital nail disorder (NDNC) being a rare subgroup inherited in autosomal dominant or autosomal recessive pattern. These are classified into ten different types (NDNC1-10), which are described in OMIM.1 The genes described for isolated nail disorders include PLCD1 (MIM 602142), RSPO4 (MIM 610573), FZD6 (MIM 603409), COL7A1 (MIM 120120), HPGD (MIM 601688) and SLCO2A1 (MIM 601460). In Addition, two other loci for NDNC have been mapped on chromosome 17p13 and 17q25.1-17q25.3.1, 2 This article is protected by copyright. All rights reserved.

Microbial and toxic metal contamination in well drinking water: potential health risk in selected areas of Kohat, Pakistan

Abstract In this study, the load of microorganisms and concentration and daily intake of toxic metals (Cu, Zn, Cd, Pb) in drinking water sources (wells) of three towns, Mian Khail (MK), Mer Ahmad Khail (MAK) and Gari Banurian (GB), in Kohat city of Pakistan were investigated. Multifactorial analysis was conducted to determine the microbial and toxic metals load in drinking water of the investigated towns. The obtained results revealed that the fecal coliform bacteria (FCB), Salmonella, Shigella and Staphylococci were the highest in MAK followed by MK and GB. The toxic metals concentrations and their intake load in the study area was in the order: Cd > Pb > Cu > Zn. However, the concentrations of toxic elements were within the permissible limits set by the Pakistan Environmental Protection Agency (PAK EPA). The study area had a higher load of enteric pathogens such as the Shigella sp., fecal coliform and Staphylococci in the potable water wells. The redundancy analysis (RDA) illustrated that total viable count TVB, Cu, Staphylococci and FCB were higher in MAK, fungi and Shigella sp. in GB and the Pb concentration was higher in MK. It is concluded that water in the study area is fecally contaminated and can cause health hazards. It is recommended that there should be a proper monitoring of water quality in the area to improve the existing quality and prevent further contamination of drinking water in the study area.

First report on molecular characterization of Leishmania species from cutaneous leishmaniasis patients in southern Khyber Pakhtunkhwa province of Pakistan

OBJECTIVE To report presence of Leishmania major in Khyber Pakhtunkhwa of Pakistan, where cutaneous leishmaniasis (CL) is endemic and was thought to be caused by Leishmania tropica only. METHODS Biopsy samples from 432 CL suspected patients were collected from 3 southern districts of Khyber Pakhtunkhwa during years 2011-2016. Microscopy on Giemsa stained slides were done followed by amplification of the ribosomal internal transcribed spacer 1 gene. RESULTS Leishmania amastigotes were detected by microscopy in 308 of 432 samples (71.3%) while 374 out of 432 samples (86.6%) were positive by ribosomal internal transcribed spacer 1 PCR. Subsequent restriction fragment length polymorphism confirmed L. tropica in 351 and L. major in 6 biopsy samples. CONCLUSIONS This study is the first molecular characterization of Leishmania species in southern Khyber Pakhtunkhwa. It confirmed the previous assumptions that anthroponotic CL is the major CL form present in Khyber Pakhtunkhwa province. Furthermore, this is the first report of L. major from a classical anthroponotic CL endemic focus identified in rural areas of Kohat district in southern Khyber Pakhtunkhwa.

Molecular detection of Leishmania species in human and animals from cutaneous leishmaniasis endemic areas of Waziristan, Khyber Pakhtunkhwa, Pakistan

Objectives: To detect Leishmania species in human patients, animal reservoirs and Phlebotomus sandflies in Waziristan, Pakistan. Methods: Tissue smears and aspirates from 448 cutaneous leishmaniasis (CL) suspected patients were analyzed. To sort out role of the reservoir hosts, skin scrapings, spleen and liver samples from 104 rodents were collected. Furthermore, buffy coat samples were obtained from 60 domestic animals. Sandflies were also trapped. All human, animals and sandfly samples were tested by microscopy, kinetoplastic PCR and internal transcribed spacer 1 (ITS1) PCR followed by restriction fragment length polymorphism for detection of Leishmania species. Results: An overall prevalence of 3.83% and 5.21% through microscopy and ITS1 PCR respectively was found. However, the statistically non-significant correlation was found between area, gender, and number of lesions. The presence of rodents, sandflies, domestic animals and internally displaced people increased the risk of CL. Using ITS1-PCR-RFLP, Leishmania tropica (L. tropica) was confirmed in 106 samples while 25 of the isolates were diagnosed as Leishmania major (L. major). Similarly, 3/104 rodents were positive for L. major and 14 pools of DNA samples containing Phlebotomus sergenti sandflies were positive for L. tropica. None of samples from domestic animals were positive for leishmaniasis. Conclusions: In the present study, L. tropica and L. major are found to be the main causative agents of CL in study area. Movement of internally displaced people from CL endemic areas presents a risk for nearby CL free areas. To the best of our knowledge, we report for the first time L. major infection in rodents (Rattus rattus) and L. tropica in Phlebotomus sergenti sandflies trapped in Waziristan, Pakistan.