Detection of metronidazole resistance in Trichomonas vaginalis using uncultured vaginal swabs.

Trichomonas vaginalis (T. vaginalis) is the most prevalent sexually transmitted infection (STI) globally. Metronidazole is the drug of choice for treating T. vaginalis infections although metronidazole-resistant T. vaginalis has been reported in clinical isolates. The purpose of this study was to determine the presence of mutations in nitroreductase genes associated with metronidazole resistance in vaginal swabs testing positive for T. vaginalis. This study included 385 human immunodeficiency virus (HIV)-positive pregnant women. Vaginal swabs were collected from consenting pregnant women and used for the detection of T. vaginalis using the TaqMan assay. From the vaginal swabs, nitroreductase genes ntr4 and ntr6 containing mutations associated with metronidazole resistance were amplified using a quantitative polymerase chain reaction (PCR) assay. To validate the PCR assay, T. vaginalis cultured isolates with known metronidazole resistance profiles were used as controls in the mutation detection assays. The prevalence of T. vaginalis in the study population was 12.2% (47/385). Mutations associated with resistance to metronidazole were detected in more than 40% of the samples tested, i.e. 21/47 (45%) and 24/47 (51%) for ntr4 and ntr6, respectively. A total of 19 samples (40%) carried mutations for both ntr4 and ntr6 genes associated with metronidazole resistance. The validation assays showed a positive correlation between phenotypic and genotypic resistance profiles. This study found a high prevalence of mutations associated with metronidazole resistance. This is concerning since metronidazole is currently used in the syndromic management of STIs in South Africa. Molecular-based assays for monitoring metronidazole resistance profiles using nitroreductase genes may serve as a feasible method for antimicrobial surveillance studies for T. vaginalis.

BV associated bacteria specifically BVAB 1 and BVAB 3 as biomarkers for HPV risk and progression of cervical neoplasia.

Background: Bacterial vaginosis (BV) is associated with high-risk HPV (hrHPV) genotypes. There is a proposed bidirectional relationship between hrHPV and vaginal microbial diversity. This study investigated the association between BV associated bacteria in women co-infected with Human immunodeficiency virus (HIV) and hrHPV. Methods: Stored cervical cytobrush samples were used for real time PCR detection of eight BV associated bacteria. Analysis of BV bacteria detected against HPV infection, socio-demographics and HIV data were conducted in R Statistical computing software of the R Core Team, 2020, version 3.6.3. Results: A total of 190 samples were analysed. A. vaginae (p <0.001) BVAB 1 (p <0.001), BVAB 2 (p =0.428), BVAB 3 (p <0.001), Lactobacillus species (p =0.016) and S. sanguinegens (p =0.007) were associated with prevalent hrHPV. Increasing CIN severity was independently associated with detection of BVAB 1 OR 1.51(95% CI: 0.42-5.55), BVAB 3 OR 2.72(95% CI:0.90-8.55) and S. sanguinegens OR 1.02(95% CI:0.37-2.80). All HPV genotypes/groups, gravida <2, A. vaginae (p =0.002) and BVAB 1 (p =0.026) were significantly associated with HPV persistence. BVAB 3, p =0.010 and HPV 16 were significantly associated with HPV reinfection. Conclusion: There is a significant association of A. vaginae, BVAB 1, BVAB 3, S. sanguinegens and Lactobacillus spp to prevalent hrHPV. BVAB 1, BVAB 3 and S. sanguinegens had an increased odds for increasing CIN severity. A vaginae, BVAB 1, gravida and all the HPV genotypes/groups were significantly associated with HPV persistence. Only BVAB 3 and HPV 16 were significantly associated with hrHPV reinfection at 1 year review. BVAB 1 and BVAB 3 are possible biomarkers for HPV infection and CIN progression.

Significant Associations between Chlamydia trachomatis and Neisseria gonorrhoeae Infections in Human Immunodeficiency Virus-Infected Pregnant Women.

There is a lack of data on the burden of Chlamydia trachomatis and Neisseria gonorrhoeae among human immunodeficiency virus- (HIV-) infected pregnant women in South Africa. We conducted a cross-sectional study which included 385 HIV-infected pregnant women attending antenatal clinic at the King Edward VIII Hospital in Durban, South Africa. The women provided vaginal swabs which were tested for C. trachomatis and N. gonorrhoeae. The prevalence of the individual STIs was as follows: C. trachomatis (47/385, 12.2%) and N. gonorrhoeae (16/385, 4.1%). Having a circumcised partner, testing positive for N. gonorrhoeae, and perceiving themselves of being at risk for infection were shown to increase the risk for C. trachomatis infection. Without controlling for the other factors, testing positive for N. gonorrhoeae increased the risk for C. trachomatis infection by 10-fold (OR: 10.17, 95% CI: 3.39-29.66, p < 0.001). Similarly, adjusting for the other factors, the risk for C. trachomatis infection in women who tested positive for N. gonorrhoeae was 9-fold (OR: 9.16, 95% CI: 2.19-40.18, p = 0.003). The following factors were associated with the increased risk of N. gonorrhoeae infection: not knowing their partner's HIV status, partner having other partners, and C. trachomatis infection status. Without controlling for the other factors, testing positive for C. trachomatis increased the risk for N. gonorrhoeae infection by 6-fold (OR: 6.52, 95% CI: 2.22-18.49, p < 0.001). Similarly, adjusting for the other factors, the risk for N. gonorrhoeae infection in women who tested positive for C. trachomatis was 6-fold (OR: 6.09, 95% CI: 1.73-22.03, p = 0.005). We found a significant association between C. trachomatis and N. gonorrhoeae in the pregnant women and the risk factors associated with these pathogens. Future studies are urgently required to investigate the impact of C. trachomatis/N. gonorrhoeae coinfections in HIV pregnant women since this data is lacking in our setting. In addition, etiological screening of C. trachomatis and N. gonorrhoeae during antenatal clinic is urgently required to prevent adverse pregnancy and birth outcomes associated with these infections.

Kidney transplantation in children in KwaZulu-Natal, South Africa.

BACKGROUND: CKF is an overwhelming illness, especially in children. Kidney transplantation is considered the definitive management of CKF. It has substantial benefits, including increased patient survival, improved skeletal growth, social adjustment, neuropsychological development, and better quality of life compared to chronic dialysis. METHODS: This is a retrospective, clinical, observational study in 13 children ≤16 years old who underwent kidney transplantation at IALCH in KwaZulu-Natal, South Africa, from May 2015 to December 2019. RESULTS: Over 4 years and 7 months, 13 kidney transplants were performed; 7 (53.8%) were males, and 6 (46.2%) were females. Eleven (84.6%) were Black African and 2 (15.4%) Indian children. The mean age ± (SD) of transplantation was 10.1 ± 2.8 years (range 5.8-15.8). Eight (61.5%) children were from a rural setting. The mean ± (SD) duration of follow-up was 29.5 ± 15.9 months. All kidney transplants done were from live related donors; 8 (61.5%) were parents of the recipients. None were pre-emptive transplants. Graft loss occurred in 2 (15.4%) children with 100% patient survival. Two (15.4%) children developed acute rejection. CONCLUSIONS: The commissioning of transplant services in KwaZulu-Natal, South Africa, has improved access to this modality of treatment, particularly in our Black African patients. The significant limitations we experienced were a shortage of cadaveric donors and resource limitations with no dedicated transplant unit for pediatric patients together with staffing constraints. Enhancing patient and healthcare personal education will hopefully overcome cultural and religious barriers to organ donation.

Lack of association between Mycoplasma hominis and Trichomonas vaginalis symbiosis in relation to metronidazole resistance.

Resistance mechanisms of Trichomonas vaginalis to metronidazole are still not well understood. It has been shown that Mycoplasma hominis has the ability to establish an endosymbiotic relationship with T. vaginalis. This study investigated the association between T. vaginalis and M. hominis symbiosis in relation to metronidazole resistance. This study included 362 pregnant women from the King Edward VIII hospital in South Africa. The women provided self-collected vaginal swabs for the diagnosis of T. vaginalis by culture. Metronidazole susceptibility using the broth-microdilution assay was performed. Detection of the 16S rRNA from M. hominis using T. vaginalis genomic DNA as the template was performed. All statistical analysis was conducted in R statistical computing software. A total of 21 culture positive isolates were obtained resulting in a prevalence of 5.8% for T. vaginalis in the study population. Under anaerobic incubation, 52.4% (11/21) of the isolates were susceptible to metronidazole (MIC ≤ 1 µg/ml). Intermediate resistance (MIC of 2 µg/ml) and full resistance (4 µg/ml) was observed in 38.1% (8/21) and 9.5% (2/21) of the isolates, respectively. The majority of the isolates 95% (19/20) were susceptible to metronidazole under aerobic conditions. Only one isolate had a MIC of 50 µg/ml. M. hominis was shown to be present in 85.7% (18/21) of the T. vaginalis isolates. However, there was no significant association between metronidazole susceptibility and T. vaginalis-M. hominis symbiosis. This study provides evidence of emerging metronidazole resistance in T. vaginalis. However, these resistance profiles were not associated with M. hominis symbiosis.

Prevalence of Genotypes and Subtypes of Gardnerella vaginalis in South African Pregnant Women.

Background: Gardnerella vaginalis, a microorganism highly linked to bacterial vaginosis (BV), is understudied in terms of genotypic heterogeneity in South African populations. This study investigated the prevalence of G. vaginalis genotypes in BV-positive, BV-intermediate, and BV-negative South African pregnant women. Methods: The study population included n = 354 pregnant women recruited from a public hospital in Durban, South Africa. The women provided self-collected vaginal swabs for BV diagnosis by Nugent scoring. For the genotyping assays, the 16S rRNA and sialidase A genes from BV-negative, BV-intermediate, and BV-positive samples were amplified with G. vaginalis-specific primers. The16S rRNA amplicon was digested with TaqI to generate genotyping profiles, and subtypes were determined by correlating BamHI and HindIII digestion profiles. Phylogenetic analysis was performed on the 16S rRNA and sialidase A sequences. The data analysis was performed with R Statistical Computing software, version 3.6.2. Results: Two different genotypes, GT1 and GT2, were detected. The most prevalent genotype was GT1. Four subtypes (1, 2B, 2AB, and 2C) were shown to be present. The most prevalent subtype was 2B, followed by subtypes 1, 2C, and 2AB. The phylogenetic analysis of the 16S rRNA showed the presence of 5 clusters. The tree displayed clusters which contained sequences from the same BV group with different genotypes and subtypes. Clusters with sequences from across the BV groups carrying the same genotype and subtype were present. Diversity of the sialidase A across BV groups and genotypes was observed. Finally, the study did not find a significant association (p > 0.05) between reported symptoms of abnormal vaginal discharge and genotype harboured. Conclusion: This study provided the first report on the diversity of G. vaginalis in South African pregnant women. Diversity assessments of G. vaginalis with respect to genotypes and virulence factors may aid in a greater understanding of the pathogenesis of this microorganism.

Mycoplasma hominis increases the risk for Ureaplasma parvum infection in Human immunodeficiency virus infected pregnant women.

INTRODUCTION: Mycoplasma hominis and Ureaplasma parvum have been recently linked to sexually transmitted diseases and other conditions. There are a limited number of studies conducted on South African pregnant women that have assessed the prevalence and risk factors for genital mycoplasmas. METHODOLOGY: This study included 264 HIV infected pregnant women attending the King Edward VIII antenatal clinic in eThekwini, South Africa. DNA was extracted using the PureLink Microbiome kit and pathogens were detected using the TaqMan Real-time PCR assays. The statistical data analysis was conducted in a freely available Statistical Computing Environment, R software, version 3.6.3 using the RStudio platform. RESULTS: The prevalence of M. hominis and U. parvum, was 215/264 (81.4%), and 203/264 (76.9%), respectively. In the M. hominis positive group, a significantly (p = 0.004) higher proportion, 80.5% tested positive for U. parvum infection when compared to 61.2% among the M. hominis negative. Of the U. parvum positive women, a significantly (p = 0.004) higher proportion of women (85.2%) tested positive for M. hominis when compared to 68.9% among the U. parvum negative. In the unadjusted and adjusted analysis, being M. hominis positive increased the risk for U. parvum by approximately 3 times more (p = 0.014) and 4-fold (p = 0.008), respectively. CONCLUSIONS: This study showed a significant link between M. hominis and U. parvum infection. To date, there are a limited number of studies that have investigated M. hominisbeing a risk factor for U. parvum infection. Therefore, the data presented in the current study now fills in this gap in the literature.

Prevalence of Chlamydia trachomatis infection in pregnant women from Durban, South Africa.

INTRODUCTION: The Sub-Saharan African region has some of the world's highest prevalence of sexually transmitted infections (STIs). These infections are considered a major public health concern. Previous studies on the prevalence of C. trachomatis infection in Sub-Saharan Africa have reported rates ranging from 3.1% to 36.8% in pregnant women. This study investigated the prevalence and risk factors associated with C. trachomatis infection in pregnant women. METHODS: This study included 735 stored clinical samples that were collected from pregnant women attending the antenatal clinic at King Edward VIII Hospital in Durban from 2018 -2021. C. trachomatis was detected using the Applied BiosystemsTM TaqMan® Assays from stored DNA samples. RESULTS: A total of 81/735 (11%) samples tested positive for C. trachomatis infection. The overall median (Q1-Q3) age of the women was 29.0 years (24.0-35.0). The majority of the women who tested positive for C. trachomatis were younger, median (Q1-Q3) age 26.0 years (23.0-32.0) vs 30.0 years (25.0-35.0) for the negative women (p < .001). Of the positive women, 96.3% were unmarried (p=0.014). Older women were less likely to test positive for C. trachomatis infection (OR: 0.93; 95% CI 0.89-0.96 p = .001). Women who were married (OR: 0.25; 95% CI 0.06-0.70; p = .022), co-habiting with their partner (OR: 0.60; 95% CI 0.36-0.98; p = .048) and started having sex at older than 15 years (OR:0.26; 95% CI 0.09-0.87; p = .018) were less likely to test positive for C. trachomatis compared to their counterparts. CONCLUSION: This study showed that behavioural and clinical factors were associated with prevalent infections. In order to reduce prevalent infections, stronger risk reduction counselling messages need to be provided from the educational and public health sector.

Development of a Zimbabwean child growth curve and its comparison with the World Health Organization child growth standards.

BACKGROUND: There is limited research that describes the growth trajectories of African children. The development of World Health Organization (WHO) growth standards considered a sample of children who lived in environments optimum for human growth. AIM: This study aimed to develop weight-for-age and height-for-age growth curves from the Zimbabwean 2018 National Nutrition Survey and compare them with the WHO growth standards. SETTING: Study participants were recruited from all districts in Zimbabwe. METHODS: Height-for-age and weight-for-age data collected from 32 248 children were used to develop the Zimbabwean references. Smooth growth curves (height, weight and body mass index [BMI]-for-age) were estimated with the Lambda Mu Sigma (LMS) method and compared with the WHO growth standards. RESULTS: Zimbabwean children were shorter and weighed less in comparison with the WHO growth standards. The -2 standard deviation (s.d.) Z-score curves (height-for-age) for Zimbabwean children (boys and girls) were below the -1 s.d. Z-score curves of the WHO growth standards. The Zimbabwean Z-scores (BMI-for-age) values above -1 s.d. were significantly higher in comparison with the corresponding WHO growth standards. CONCLUSION: Utilising the WHO growth standards would diagnose a higher proportion of Zimbabwean children as stunted whilst underestimating the proportion at risk of obesity. The WHO growth standards lack a consideration of the geographical, economic, political and environmental constraints existing between countries.

Low prevalence of macrolide resistance in Mycoplasma genitalium infections in a cohort of pregnant women living with human immunodeficiency virus.

OBJECTIVE: Macrolide resistance in Mycoplasma genitalium (M. genitalium) is increasing as a result of the widespread use of azithromycin in the treatment of sexually transmitted infections (STIs). To date, there are few published studies on macrolide resistance patterns in South African pregnant women. This study now contributes to the growing body of knowledge. METHODS: This study included 385 pregnant women living with HIV. Vaginal swabs were collected from consenting pregnant women and used for the detection of M. genitalium using the TaqMan assay. Macrolide resistance-associated mutations in the 23S rRNA gene were determined for all samples that tested positive for M. genitalium using the AllplexTM MG & AziR assay (Seegene) which allows for the simultaneous detection and identification of M. genitalium and six mutations (A2058C, A2058G, A2058T, A2059C, A2059G and A2059T) responsible for azithromycin resistance. The correlation between the TaqMan assay and AllplexTM MG & AziR assay (Seegene) for the detection of M. genitalium was also performed in a subset of 121 samples. RESULTS: Of the 385 samples tested in this study, 14 samples were positive for M. genitalium estimating a prevalence of 3.6%. The same 14 samples also tested positive on the AllplexTM assay indicating a good correlation between the TaqMan Assay and the AllplexTM. Of the 14 positive samples, one sample carried a mutation at position A2059G denoting macrolide resistance in this pathogen. Mutations in the other regions of the 23S rRNA were not detected. All assay controls used in the mutation scanning produced the desired results showing the validity of the assay. CONCLUSION: In this study, macrolide resistance in M. genitalium was detected. Despite the low prevalence of resistance determinants ongoing antimicrobial resistance surveillance is vital considering that azithromycin is used in the syndromic management for the treatment of vaginal discharge syndrome.

Segmented linear correlations between bone scan index and prostate cancer biomarkers, alkaline phosphatase, and prostate specific antigen in patients with a Gleason score ≥7.

ABSTRACT: Technetium-99m methyl diphosphonate bone scintigraphy is relatively easily accessible for detecting bone metastases in prostate cancer patients. However, it is subjective and can be challenging to compare images taken at different time points. The bone scan index (BSI) is a more objective evaluation and allows for better comparison of images. Its correlation with other biomarkers of prostate cancer metastases such as prostate specific antigen (PSA) and alkaline phosphatase (ALP) is not clearly understood. This study thus aimed to compare the BSI correlation to PSA against that of BSI to ALP levels in patients with a Gleason score ≥7.A retrospective analysis of the medical records of 50 prostate cancer patients with a Gleason score of ≥7 referred for a bone scan between January 1, 2015 and December 31, 2018 was undertaken. Bone scans were interpreted visually, and using a semi-automated computer programme to quantify the BSI and its relation to PSA and ALP measurements.For the metastasis positive measurements, there was a statistically significant moderate positive overall linear correlation between BSI and PSA. For ALP and BSI, there were 2 segmented strong positive linear relationships between them. The first segment consisted of ALP < 375 IU/L and BSI >10%, where ALP and BSI were strongly and positively correlated. The other segment tended to have generally low BSI measurements (<10%) and also had a strong and positive correlation.The BSI was found to be better linearly correlated with ALP than PSA.

Strong correlation between urine and vaginal swab samples for bacterial vaginosis.

BACKGROUND: Vaginal swabs have been traditionally used for the diagnosis of bacterial vaginosis (BV). Currently, there are limited studies that have investigated the use of other sample types other than vaginal swabs for the detection of BV from South African populations. This study investigated whether urine can be used for the detection of BV-associated microorganisms in South African pregnant women. METHODS: One-hundred self-collected vaginal swabs and urine samples were obtained from women presenting for antenatal care at King Edward VIII Hospital in Durban. The BD MAX™ vaginal panel assay was used for diagnosing BV and droplet digital polymerase chain reaction was used to quantify Gardnerella vaginalis, Prevotella bivia, Atopobium vaginae and Lactobacillus crispatus. The absolute counts were determined on the QX200 Droplet Reader (Bio-Rad) using the QuantaSoft Software. Data analysis was performed with statistical computing software called R, version 3.6.1. RESULTS: Median copy numbers obtained for G. vaginalis and P. bivia across urine and swabs in BV-positive samples were not significantly different (p = 0.134 and p = 0.652, respectively). This was confirmed by the correlation analysis that showed a good correlation between the two sample types (G. vaginalis [r = 0.63] and P. bivia [r = 0.50]). However, the data obtained for A. vaginae differed, and a weak correlation between urine and swabs was observed (r = 0.21). Bacterial vaginosis-negative samples had no significant difference in median copy numbers for L. crispatus across the urine and swabs (p = 0.062), and a good correlation between the sample types was noted (r = 0.71). CONCLUSION: This study highlights the appropriateness of urine for the detection of microorganisms associated with BV.

'Mycoplasma hominis does not share common risk factors with other genital pathogens': Findings from a South African pregnant cohort.

BACKGROUND: The role of Mycoplasma hominis (M. hominis) as a genital tract pathogen was still debatable. This study identified the risk factors associated with the prevalence of M. hominis in South African pregnant women. METHODS: This was a cross-sectional analysis of n = 221 prenatal patients attending a Durban hospital during November 2017 to April 2018. M. hominis was detected from urine samples using the quantitative polymerase chain reaction. The population characteristics were described using frequencies stratified by the infection status of M. hominis. In addition, a univariate analysis was used to assess the relationship between each risk factor and infection status. The analysis further considered logistic regression to assess the influence of these risk factors univariately and in the presence of other factors. The coinfection rate between M. hominis and bacterial vaginosis (BV), Trichomonas vaginalis (T. vaginalis), Mycoplasma genitalium (M. genitalium) and Candida species was also determined. All the tests were conducted at 5% level of significance. RESULTS: The prevalence of M. hominis in this study population was 48% (106/221). In the univariate analysis, factors significantly associated with M. hominis positivity included having past abnormal vaginal discharge (p = 0.037), having current abnormal vaginal discharge (p = 0.010) and a borderline significance (p = 0.052), which were noted for previous pre-term delivery. However, none of these factors were sustained in the multivariate analysis. There was a statistically significant association between M. hominis and BV positivity (p < 0.001). Similarly, M. hominis and M. genitalium positivity was significant (p = 0.006). CONCLUSION: This study showed that M. hominis does not share common risk factors with known genital tract pathogens in a population of pregnant women and therefore cannot be considered a genital tract pathogen.

Lack of resistance to macrolides in Mycoplasma genitalium detected in South African pregnant women.

BACKGROUND: Azithromycin regimens have been considered first-line treatment for Mycoplasma genitalium (M. genitalium), a sexually transmitted infection (STI) associated with adverse pregnancy outcomes. However, recent years have seen rapid emergence of macrolide resistance in M. genitalium as a result of widespread administration of azithromycin. Currently, there are limited data on macrolide resistance in pregnant women from KwaZulu-Natal (KZN), South Africa. This study investigated the prevalence of M. genitalium and emerging patterns of macrolide resistance in pregnant women from KZN. METHODS: This was a sub-study of a larger study which involved laboratory-based detection of STIs in pregnant women. In the main study, pregnant women provided urine samples for detection of STIs. For this study, deoxyribose nucleic acid (DNA) extracted from stored urine was used to determine emerging macrolide resistance by amplification of the 23S ribosomal ribonucleic acid (rRNA) gene of M. genitalium by polymerase chain reaction (PCR) and sequencing of amplicons to identify mutations associated with resistance. The Allplex™ MG & AziR assay was used as a confirmatory assay. RESULTS: The prevalence of M. genitalium in pregnant women was 5.9% (13 out of 221). Sequencing of PCR amplicons did not reveal the presence of the A2059G and A2058G mutations associated with macrolide resistance. These findings were confirmed by the Allplex™ MG & AziR assay. CONCLUSION: Despite the lack of resistance to macrolides in this study population, continued antimicrobial resistance surveillance for M. genitalium in pregnant women is important because azithromycin is now part of the South African national STI syndromic management guidelines for vaginal discharge syndrome.

Comparison of methods for the detection of Neisseria gonorrhoeae from South African women attending antenatal care.

The detection of Neisseria gonorrhoeae using culture assays is challenging. This study aims to compare different assays for the detection of N. gonorrhoeae. This cross-sectional study was conducted at King Edward VIII Hospital and included 307 antenatal attendees, each willing to provide two endocervical swabs. The first swab was used for culture identification of N. gonorrhoeae, and the second swab was processed for the detection of the pathogen by the TaqMan quantitative polymerase chain reaction (qPCR) assay, an in-house 16S ribosomal RNA (rRNA) PCR and PCR detection of the opa gene. Culture and the nucleic acid amplification assays were each used as comparator tests in the analysis. Sensitivity and specificity were calculated using RS Studio. The prevalence of N. gonorrhoeae was 7.8%. When compared to the TaqMan assay, the 16S rRNA PCR exhibited the highest sensitivity of 62%, with a substantial level of agreement (kappa level of agreement: 0.60), followed by the opa PCR (38%) with a moderate level of agreement (0.52) and culture exhibiting the lowest sensitivity of 25% with a fair level of agreement (0.38). The diagnostic accuracy of all the assays was >90%. The TaqMan qPCR assay has the ability to serve as a future diagnostic assay for the detection of N. gonorrhoeae.

Scintigraphic peritoneography in the diagnosis of pleuroperitoneal leak complicating peritoneal dialysis: A comparison with conventional diagnostic methods.

A pleuroperitoneal leak (PPL) is a relatively rare complication of peritoneal dialysis (PD) and early diagnosis is essential.Patients suspected of a PPL usually present with dyspnea (marked during inflow of PD fluid) and tend to have transudative high glucose pleural effusions.The PPL scintigraphy (PPLS) is one of the methods for objectively proving a PPL. The effectiveness of PPLS as a noninvasive method of evaluating a suspected PPL and its effectiveness in the exclusion of a leak in patients with similarly presenting comorbidities was assessed.Patients suspected to have a PPL were considered for PPLS based on clinical presentation and pleural fluid analysis. Radiopharmaceutical was administered into the peritoneum via the dialysis port with the patient lying supine and immediate dynamic followed by delayed statics were acquired.Of the 27 scans reviewed, 70% were found to be positive with majority detected within 12 minutes of radiopharmaceutical administration with a high predominance occurring in the right chest (P < .001). In PPLS-positive patients, when both chest X-rays and planar agreed on showing the right-sided chest predominance, the highest measurements of the pleural glucose:serum glucose ratio were recorded. A statistically significant correlation between the outcome of the scan and final decision on patient management was noted (P < .01).The PPLS is an effective diagnostic tool for assessing PPLS. However, multicenter studies investigating its added value over other conventional methods are needed to establish it as a highly relevant diagnostic tool.

Trends and Adaptive Optimal Set Points of CD4+ Count Clinical Covariates at Each Phase of the HIV Disease Progression.

In response to invasion by the human immunodeficiency virus (HIV), the self-regulatory immune system attempts to restore the CD4+ count fluctuations. Consequently, many clinical covariates are bound to adapt too, but little is known about their corresponding new optimal set points. It has been reported that there exist few strongest clinical covariates of the CD4+ count. The objective of this study is to harness them for a streamlined application of multidimensional viewing lens (statistical models) to zoom into the behavioural patterns of the adaptive optimal set points. We further postulated that the optimal set points of some of the strongest covariates are possibly controlled by dietary conditions or otherwise to enhance the CD4+ count. This study investigated post-HIV infection (acute to therapy phases) records of 237 patients involving repeated measurements of 17 CD4+ count clinical covariates that were found to be the strongest. The overall trends showed either downwards, upwards, or irregular behaviour. Phase-specific trends were mostly different and unimaginable, with LDH and red blood cells producing the most complex CD4+ count behaviour. The approximate optimal set points for dietary-related covariates were total protein 60-100 g/L (acute phase), <85 g/L (early phase), <75 g/L (established phase), and >85 g/L (ART phase), whilst albumin approx. 30-50 g/L (acute), >45 g/L (early and established), and <37 g/L (ART). Sodium was desirable at approx. <45 mEq/L (acute and early), <132 mEq/L (established), and >134 mEq/L (ART). Overall, desirable approximates were albumin >42 g/L, total protein <75 g/L, and sodium <137 mEq/L. We conclude that the optimal set points of the strongest CD4+ count clinical covariates tended to drift and adapt to either new ranges or overlapped with the known reference ranges to positively influence the CD4+ cell counts. Recommendation for phase-specific CD4+ cell count influence in adaptation to HIV invasion includes monitoring of the strongest covariates related to dietary conditions (sodium, albumin, and total protein), tissue oxygenation (red blood cells and its haematocrit), and hormonal control (LDH and ALP).

Covariate random effects on the CD4 count variation during HIV disease progression in women.

Purpose: To investigate the variation in CD4 count between HIV positive patients due to clinical covariates at each phase of the HIV disease progression. Patients and methods: The Centre for the AIDS Programme of Research in South Africa (CAPRISA) conducted different studies in which female patients were initially enrolled in HIV negative cohorts (phase 1). Seroconverts were further followed-up weekly to fortnightly visits up to 3 months (phase 2: acute infection), monthly visits from 3 to 12 months (phase 3: early infection), quarterly visits thereafter (phase 4: established infection) until antiretroviral therapy (ART) initiation (phase 5). Results: Eighteen out of the 46 CD4 count covariates investigated were significant. Low average CD4 counts at acute and early phase entry improved at a faster rate than entries at higher average CD4 count. During therapy, all the 18 covariates induced significantly different patients' average CD4 counts. The rate of change of CD4 count greatly varied in response to lactate dehydrogenase during the acute phase. Red blood cells increase resulted in the patients' CD4 counts approaching a common higher level during the early phase. During therapy, the already high CD4 counts improved faster than lower ones in response to the red blood cells increase. As the monocytes increased, patients with lower average CD4 counts became worse than those with higher average CD4 counts. Conclusion: Changes in the covariates measurements either induced no variation effects in certain phases or improved the CD4 count at a faster rate for those patients whose average CD4 was already high or worsen the CD4 level which was already low or caused the patients' CD4 counts to approach the same level - higher or lower than the general cohort. The studied covariates induced wide variations in the CD4 count between HIV positive patients during the ART phase.

An Evaluation to Determine the Strongest CD4 Count Covariates during HIV Disease Progression in Women in South Africa.

INTRODUCTION: Past endeavours to deal with the obstacle of expensive Cluster of Difference 4 (CD4+) count diagnostics in resource-limited settings have left a long trail of suggested continuous CD4+ count clinical covariates that turned out to be a potentially important integral part of the human immunodeficiency virus (HIV) treatment process during disease progression. However, an evaluation to determine the strongest candidates among these CD4+ count covariates has not been well documented. METHODS: The Centre for the AIDS Programme of Research in South Africa (CAPRISA) initially enrolled HIV-negative (phase 1) patients into different study cohorts. The patients who seroconverted (237) during follow-up care were enrolled again into a post-HIV infection cohort where they were further followed up with weekly to fortnightly visits up to 3 months (phase 2: acute infection), monthly visits from 3-12 months (phase 3: early infection) and quarterly visits thereafter (phase 4: established infection) until antiretroviral therapy (ART) initiation (phase 5). The CD4+ count and 46 covariates were repeatedly measured at each phase of the HIV disease progression. A multilevel partial least squares approach was applied as a variable reduction technique to determine the strongest CD4+ count covariates. RESULTS: Only 18 of the 46 investigated clinical attributes were the strongest CD4+ count covariates and the top 8 were positively and independently associated with the CD4+ count. Besides the confirmatory lymphocytes, these were basophils, albumin, haematocrit, alkaline phosphatase (ALP), mean corpuscular volume (MCV), platelets, potassium and monocytes. Overall, electrolytes, proteins and red blood cells were the dominant categories for the strongest covariates. CONCLUSION: Only a few of the many previously suggested continuous CD4+ count clinical covariates showed the potential to become an important integral part of the treatment process. Prolonging the pre-treatment period of the HIV disease progression by effectively incorporating and managing the covariates for long-term influence on the CD4+ cell response has the potential to delay challenges associated with ART side effects.