Evolution of HBV S-gene in the backdrop of HDV co-infection.

HBV-HDV co-infected people have a higher chance of developing cirrhosis, fulminant hepatitis, and hepatocellular carcinoma (HCC) compared to those infected only with HBV. The present study was conducted to investigate HBV genotypes and phylogeny among HBV mono-infected and HBV-HDV co-infected patients, as well as analyze mutations in the surface gene of HBV in mono-infected and co-infected patients. A total of 100 blood samples (50 co-infected with HBV and HDV, and 50 mono-infected with HBV only) were collected for this study. HBV DNA was extracted from patient sera and partial surface antigen gene was amplified from HBV genome using polymerase chain reaction. HBV S gene was sequenced from 49 mono-infected and 36 co-infected patients and analyzed to identify HBV genotypes and phylogenetic patterns. Subsequently, HBV S amino acid sequences were analyzed for mutational differences between sequences from mono- and co-infected patients. HBV genotype D was predominantly found in both mono-infected as well as co-infected patients. Phylogenetic analysis showed the divergence of HBV sequences, between mono- and co-infected patients, into two distinct clusters. HBV S gene mutation analysis revealed certain mutations in HBV-HDV co-infected subjects to be distinct from those found in mono-infected patients. This might indicate the evolution of HBV S gene under selection pressures generated from HDV coinfection.

HIV among women and children in Pakistan.

The HIV epidemic in Pakistan has now transmitted to female spouses of HIV-positive injection drug users (IDUs) and bisexual men, and to preadolescent children through vertical transmission. Owing to sociocultural barriers, HIV-infected pregnant women and children do not have optimum access to treatment, hindering the prevention of HIV transmission.

Population-specific evolution of HIV Gag epitopes in genetically diverged patients.

BACKGROUND: Under the host selection pressure HIV evolves rapidly to override crucial steps in the antigen presentation pathway. This allows the virus to escape binding and recognition by cytotoxic T lymphocytes. Selection pressures on HIV can be unique depending on the immunogenetics of host populations. It is therefore logical to hypothesize that the virus evolving in a given population will carry signature mutations that will allow it to survive in that particular host milieu. OBJECTIVES: The aim of this study was to perform a comparative analysis of HIV-1 Gag subtype A sequences from two genetically diverged populations, namely, Kenyan and Pakistani. We analyzed unique mutations that could intercept the antigen processing pathway and potentially change the repertoire of Gag epitopes in each study group. METHODS: Twenty-nine Kenyan and 56 Pakistani samples from HIV-1 subtype A-infected patients were used in this study. The HIV-1 gag region p24 and p2p7p1p6 was sequenced and mutations affecting proteasomal degradation, TAP binding, HLA binding and CTL epitope generation, were analyzed using the in silico softwares NetChop and MAPPP, TAPPred, nHLAPred and CTLPred, respectively. RESULTS: Certain mutations unique to either Pakistani or Kenyan patients were observed to affect sites for proteasomal degradation, TAP binding, and HLA binding. As a consequence of these mutations, epitope pattern in these populations was altered. CONCLUSION: Unique selection pressures can steer the direction of viral epitope evolution in the host populations. Population-specific HIV epitopes have to be taken into account while designing treatment as well as vaccine for HIV.

The spread of HIV in Pakistan: bridging of the epidemic between populations.

In the last two decades, 'concentrated epidemics' of human immunodeficiency virus (HIV) have established in several high risk groups in Pakistan, including Injecting Drug Users (IDUs) and among men who have sex with men (MSM). To explore the transmission patterns of HIV infection in these major high-risk groups of Pakistan, 76 HIV samples were analyzed from MSM, their female spouses and children, along with 26 samples from a previously studied cohort of IDUs. Phylogenetic analysis of HIV gag gene sequences obtained from these samples indicated a substantial degree of intermixing between the IDU and MSM populations, suggesting a bridging of HIV infection from IDUs, via MSM, to the MSM spouses and children. HIV epidemic in Pakistan is now spreading to the female spouses and offspring of bisexual MSM. HIV control and awareness programs must be refocused to include IDUs, MSM, as well as bisexual MSM, and their spouses and children.

Patterns of HIV infection among native and refugee Afghans.

The current study was conducted to explore the origins of the HIV epidemics among the Afghan refugees in Pakistan and the native Afghans in Afghanistan. Phylogenetic analysis of HIV gag gene from 40 samples showed diverse HIV variants, originating from a number of countries. Intermixing of diverse HIV variants among Afghans may give rise to seeding of infections with rare HIV strains which may pose serious challenges for the treatment and control of infection.

A wide spectrum of dengue IgM and PCR positivity post-onset of illness found in a large dengue 3 outbreak in Pakistan.

During a large outbreak of dengue serotype 3 in Pakistan in 2006, multiple serum samples were routinely collected for laboratory testing. Two hundred ninety-seven samples were collected between August and November 2006. Serological testing for dengue IgM was performed in Pakistan and polymerase chain reaction (PCR) testing for dengue RNA detection and serotyping were performed in Hong Kong. Dengue-specific IgM was detectable as early as 1 day, and dengue RNA remained detectable for up to 14 days, post-onset of illness. Further statistical analysis found that IgM status (positive, negative, or equivocal) was significantly correlated to clinical (duration of illness, severity of patient-reported arthralgia pain, the presence of any evidence of bleeding, a positive tourniquet test, shock), and other laboratory (platelet and total white cell counts) parameters. In contrast, the qualitative dengue RNA status (PCR positive or negative) was not statistically significantly correlated with any of these other parameters. The results for this population during this outbreak, obtained from single acute samples, demonstrate a wide range of intervals post-onset of illness during which dengue IgM and dengue RNA may be detected. Interestingly, in this study, the dengue IgM positivity correlates more closely with significant clinical illness than the dengue RNA positivity, which may be a feature specific to this particular outbreak.