Asad Zia

Tick-borne viruses (TBVs) pose significant public health and economic threats. Pakistan has endemic Crimean-Congo hemorrhagic fever virus (CCHFV), but evidence suggests broader TBV circulation. This study assessed the seroprevalence of thirteen TBVs (seven are members of the genus Orthonairovirus and six are members of the genus Bandavirus) in humans, livestock, and rats in Punjab, Pakistan. Serum samples (n = 794: 321 livestock, 253 human, and 220 rat) were collected from the Narowal, Lahore, and Faisalabad districts. Antibodies to viral NPs were detected using the luciferase immunoprecipitation system (LIPS). The overall seroprevalence was 19.14% (152/794); it was highest in livestock (27.10%), then humans (20.55%), and then rats (5.91%). The highest seroprevalence rates were 3.12% for CCHFV in livestock, 3.56% for Yezo virus (YEZV) in humans, and 0.91% for Tamdy virus (TAMV) and Tacheng tick virus 1 (TcTV-1) in rats. Neutralizing antibodies were detected against CCHFV (1 cattle, 4 humans), Bhanja virus (BHAV) (3 livestock, 1 rat), TAMV (1 cattle), Guertu virus (GTV) (1 cattle), and Dabie bandavirus (2 cattle). Sixteen samples showed antibodies to both orthonairoviruses and bandaviruses, indicating co-exposure. Further analysis showed that seropositivity was not randomly distributed. Livestock kept in commercial farming systems and people working mainly outdoors had distinctly higher exposure to TBVs than subsistence livestock and indoor workers. The results supported the circulation of TBVs among hosts within the close socio-economic/ecological integration area of Pakistan. These findings confirm the circulation of CCHFV, SFTSV, GTV, and TAMV; provide the first serologic evidence of BHAV in Pakistan; and underscore the need for further investigation into the potential circulation of additional TBVs. All results demonstrated that multiple TBVs have been circulating among humans, livestock, and rodents in Pakistan.

Crimean-Congo hemorrhagic fever (CCHF) is a widespread tick-borne zoonotic disease. Sporadic outbreaks of CCHF occur in endemic regions, including Pakistan. The clinical spectrum of the illness varies from asymptomatic seroconversion to severe disease which may end in death. The treatment is supportive, including blood and blood products. There is multi-organ involvement in CCHF including acute hepatitis, thrombocytopenia, coagulopathy, acute kidney injury (AKI), and encephalopathy. Hematological and biochemical parameters may identify patients at substantial risk of worse outcomes. Early detection of the disease and forecasting the clinical course may be helpful. This case series aims to evaluate the trends of hematological and biochemical parameters among the survivors and non-survivors of CCHF. All consecutive patients aged 16 years and above admitted to the isolation unit of Hayatabad Medical Complex, Peshawar, Pakistan between 1^st July and 30^th July 2022 with the diagnosis of CCHF were included in this case series. The diagnosis of CCHF was made by detecting viral ribonucleic acid by a polymerase chain reaction. For all patients, age, gender, address, occupation, clinical presentation, history of contact with animals, and travel history were recorded. All the vitals were taken regularly. The hematological (complete blood count) and biochemical parameters (serum creatinine, alanine aminotransferase (ALT), and C-reactive protein (CRP)) were documented daily. The blood group was determined for all the cases. Out of 17 cases, the majority (16 cases, 94.1%) were male and butchers (eight cases, 47.1%) by profession. All cases had significant contact with animals. Four patients (23.5%) died. Three out of the four non-survivors (75%) had ALT < 5 times the upper limit of normal with a static pattern of liver enzymes without much decline in ALT till death. One non-survivor (25%) had marked elevation of ALT at presentation, which had a declining trend till death. Seven out of 13 survivors (53.8%) had moderate to marked elevation in the level of ALT at presentation. The ALT showed a downward trend during the course of illness in all these patients. The remaining survivors (six out of 13, 46.2%) had a mild elevation of ALT and 50% of them showed improvement in the ALT level during hospitalization. All patients had thrombocytopenia at presentation. None of the non-survivors showed a persistent increase in the platelet count, and three cases remained severely thrombocytopenic at the time of death. However, the trend in platelet count among all the survivors was increasing. The CRP level in the majority (three out of four cases, 75%) of the non-survivors remained elevated till death, while all survivors showed a progressive decline in CRP level. A majority (11 out of 17 cases) had blood group B. Half of the non-survivors (two out of four cases) and the majority of the survivors (nine out of 13 cases) had blood group B. AKI was found in all non-survivors, while all the survivors had normal renal function throughout the course. A persistently raised ALT and CRP level, a persistently low or decreasing platelet count, and AKI were associated with mortality. Blood group B was the commonest blood group among patients of CCHF, which is not reflective of the blood group distribution of the general population from which this case series has been reported.

Approximately 10 million people in Pakistan are infected with the hepatitis C virus (HCV). Most patients develop chronic hepatitis, with rare cases of spontaneous clearance. However, little is known about multidrug resistant viral variants in Pakistan. This case study describes a 47-year-old male diagnosed with chronic HCV genotype 3a infection in 2003. After an initial diagnosis of viral infection, the patient remained treatment naïve for 5 years. He received two therapy cycles of interferon (IFN) plus ribavirin (RBV) in 2007 and 2010, however, he was non-responsive to the therapy. The patient then received an additional two treatment cycles of pegylated IFN α-2b plus RBV (in 2011 and 2013); he was still non-responsive. In 2016, the patient underwent sofosbuvir plus RBV combination therapy, however, the sustained virological response was still not achieved. The host genetic factor was found to be heterozygous guanine and thymine (GT) and cytosine and thymine (CT) genotypes of rs8099917 and rs12979860 polymorphism of IL28B, respectively. Phylogenetic analysis suggests that the resistant variant belong to an out-group and may require triple therapy. This is the first case that reports on a HCV-infected individual who was a non-responder to multiple IFN therapies in Pakistan. Further studies are needed to understand multidrug-resistant HCV variants in the Pakistani population.