Sexually transmitted infection (STI) cases across the world are an ever present and ever-increasing issue, not only to adults but to a foetus. Two diseases of particular importance are HIV and Syphilis (caused by the bacterium Treponema pallidum).

How big a threat are STIs in today’s world?

The most recent figures show that in the US, Syphilis cases have tripled between 2013 and 2018 , which includes 5,726 pregnant women. Between 2008 and 2018 Europe also saw a 50% increase in Syphilis and Canada’s cases have more than doubled. In these high-income countries men are disproportionately  affected, however, in low to middle income countries (LMIC), syphilis is endemic to the general population and makes up over 90% of worldwide case numbers. This also means high numbers of infections in pregnant women, leading to increased cases of congenital Syphilis.

Syphilis is classed as an ulcerative STI, which means it causes genital ulcers. These ulcers facilitate the acquisition of HIV during intercourse, increasing the chance of transmission five-fold. Coinfections of Syphilis and HIV can increase the HIV viral load and HIV can accelerate the natural history of Syphilis. This means that individuals suffering from a coinfection will more frequently develop neurosyphilis than those with syphilis alone. In LMIC countries such as Tanzania, Uganda, and Ethiopia, the number of HIV positive patients with Syphilis are nearly 10%, and in Ghana, it is as high as 14.8%.

Source: UNAIDS WHO

What does Syphilis mean for pregnant women?

Globally, Congenital syphilis is the second leading cause of preventable stillbirths and there are a plethora of other complications that can arise from untreated congenital Syphilis, such as severe anaemia, jaundice, and ultimately blindness and deafness. In 2016, the World Health Organisation (WHO) estimated that there were 661,000 infants born with congenital Syphilis, and that approximately 40% of babies born to untreated Syphilis, or an estimated 143,000 infants, will suffer early deaths or stillbirths. This is not to say that this is inevitable, and in fact syphilis can be effectively treated with penicillin if caught early enough. This is why testing pregnant women for these infections is so important.

The World Health Organisation (WHO) ‘Prevention of Mother-to-Child Transmission of HIV/AIDS Program’ (PMTCT) aims to eliminate mother-to-child transmission of HIV and syphilis by providing technical support to member states on the uptake of antenatal services like HIV and Syphilis testing, as well as collecting and analysing regional trends.

In higher income countries, high sensitivity and high specificity tests for HIV and Syphilis are performed in labs and protocols are defined for screening of these diseases. In LMIC’s, there are often limited centralised health services or appropriate lab availability for these kinds of tests and so a point of care (POC) approach is taken, which allows for the collecting of a sample, and testing to be conducted in a single visit. POC tests for HIV have proved successful in LMIC countries, with 70-100% of pregnant women being screened. However, there is a clear deficit for pregnant women being screened for Syphilis, falling short at 40-60%. The high prevalence of syphilis in HIV infected patients indicates that there is a need to increase syphilis testing efforts.

What can be done to bridge the gap between HIV and Syphilis testing rates?

There are several combined HIV/ Syphilis POC rapid diagnostic tests (RTD) which aim to increase the rate of syphilis testing by leveraging existing HIV testing programs. To be successful the combined tests must be affordable, easy to use, and appropriate for a POC scenario. The widespread distribution of these combined tests is cheaper and more efficient than two individual tests and can allow for the early detection and treatment of HIV and Syphilis, saving both pregnant women and their unborn children.

Source: World Health Organization

Tests designed with decentralised testing and POC scenarios in mind can be visually interpreted and are easily used. Storage and distribution are big concerns and so these HIV/ syphilis POC tests are compact, have a 2-year shelf life, and can be stored across a broad temperature range. It is important to understand that these tests are only for initial screening, and if positives come back more specific alternative diagnosis methods should be used.

The importance of dual HIV/ Syphilis POC tests in LMIC’s cannot be understated. These tests are projected to allow for an additional 4.4 million women to be tested, with at least 285,000 Syphilis infections in women to be identified. Ultimately this could lead to 38,000 fewer cases of congenital syphilis, and 51,500 child mortalities being avoided.

HIV/ Syphilis Serum and Plasma from Logical Biological

Logical Biological provide a large portfolio of HIV and syphilis serum and plasma products. Testing can be performed on syphilis serum and syphilis plasma using a wide selection of methodologies including TPHA, ELISA and EIA. Available testing for HIV serum and HIV plasma includes LIA, EIA, PCR (copies/ml), Nucleic Acid Amplification, Western Blot, Ratio CD4/CD8 profiling and Chemiluminescent Immunoassay (ChLIA) (S/CO units).

All serum and plasma specimens can be provided according to your custom specifications and are supplied with demographic information available.

Table: HIV and Syphilis serum and plasma available from Logical Biological

BK polyomovirus (BKV) is a double stranded DNA virus that affects 65-90% of the adult population. Commonly a childhood infection with minimal symptoms, this virus can exist in a latent form in the renal system for a lifetime. Its significance arises if an individual becomes immunocompromised such as for recipients of kidney or bone marrow (stem cell hematopoietic) transplants (HCT). Under these circumstances tests for BKV are essential to prevent haemorrhagic cystitis, ureteral stenosis or nephropathy (BKVN) and organ rejection.

 

The kidney is the most common type of transplanted organ. There were 2,263 kidney transplant procedures in the UK in 2021/2022 and the US reached a record high of 25,487 in 2021. Bone marrow or stem cell transplant numbers are in the region of almost 5,000 people in the US, 4,000 annually in the UK and over 32,000 across Europe as a whole. With BKV affecting up to 15% of transplant patients and a lack of effective antiviral therapies, post-transplant screening is a key recommendation to manage the reduction of immunosuppression in patients with BKV infections.

 

BKV Screening

Although a kidney biopsy remains the gold standard for BKVN diagnosis, most testing is currently performed in regional or reference laboratories utilising serum, plasma, EDTA whole blood, or urine samples tested using PCR based tests. When triggered by reduced immunity, BKV reactivation causes decoy cells and viral components to be excreted in urine, viruria, then progresses across the interstitium and within a couple of weeks pass into the capillaries causing viremia.

 

In HCT patients, BKV testing can help to manage the diagnosis and management of hemorrhagic cystitis, with an antiviral drug. In kidney transplantation, screening for BKV DNA allows for an early intervention generally with a preemptive reduction in immunosuppression. This prevents BKVN development and subsequent graft failure.

 

A UK study that screened paediatric transplant patients found that 30% of them were BKV viremia positive and BKVN was found in 6.6% of cases 3 months post-transplant. This supports other studies in adults that have seen viruria and viremia from 3 months post-transplant. As a result of this, the current guidelines  for testing start at one month post-transplant, with monthly plasma screening for the first 6 months, then every 3 months until 2 years post-transplant.

 

 Image: Other kidney disease state serum and plasma available from Logical Biological

 

BKV Test Standardisation

Disparity in sample type, DNA extraction techniques, primer and probe sequences, and even the BK strain DNA used for the control, can all affect results and potentially produce clinical variability. Attempts at reducing these discrepancies have resulted in a WHO International standard to help reduce inter assay variability.

 

Introduced in 2016 the 1st WHO International Standard for BKV nucleic acid amplification testing (NAAT) enables worldwide harmonization of results across hospitals and institutions. As clinical laboratories worldwide use assays traceable to the WHO International standard, we will see an increased potential for establishing quantitative BKV DNA load cutoffs that can be used in a clinical setting. There is currently no definitive viral load cutoff associated with nephropathy although guidelines recommend a plasma viral load of ≥10,000 copies/ml as the threshold for clinical intervention in kidney transplantation based on a specificity of 93% for BKVN, some centers have reported that this threshold may underestimate the diagnosis of BKVN and suggest using lower viral load thresholds.

 

To make matters more complicated there are 12 subtypes/subgroups of BKV. Commercial diagnostic testing often uses genotype I, the Dunlop strain, as the reference sequence for primers and probes. One study looked at using these tests on BK variants and concluded a decrease in the sensitivity for patients with BKV variant infections. They urged caution when interpreting test results and being faced with a clinical discrepancy. Unfortunately, rare subtypes have been shown to be an increased risk factor for BKV induced nephropathy, namely subtypes III and IV.

 

BKV infections continue to be the predominant clinical issue faced by transplant providers and patients. Screening guidelines have resulted in earlier detection, improved patient outcomes and standardisation is helping reduce inter-assay variability. BKVN is however still a challenge for physicians, especially with no anti-viral currently available for the virus.

 

BK Virus Serum and Plasma from Logical Biological

Logical Biological provide BK Virus PCR positive serum and BK Virus PCR positive plasma with known values (IU/mL) standardised against the 1st WHO International Standard for BK Virus. We can also offer transplant serum and transplant plasma, and kidney failure samples. All serum and plasma specimens can be provided according to your custom specifications and are supplied with demographic information available.