Christa Kasang

HIV Drug Resistance (HIVDR) in Antiretroviral Therapy-Naïve Patients in Tanzania not Eligible for WHO Threshold HIVDR Survey is Dramatically High.

Background The World Health Organization (WHO) has recommended guidelines for a HIV drug resistance (HIVDR) survey for resource-limited countries. Eligibility criteria for patients include age below 25 years in order to focus on the prevalence of transmitted HIVDR (tHIVDR) in newly-infected individuals. Most of the participating sites across Africa have so far reported tHIVDR prevalences of below 5%. In this study we investigated whether the rate of HIVDR in patients <25 years is representative for HIVDR in the rest of the therapy-naïve population. Methods and Findings HIVDR was determined in 88 sequentially enrolled ART-naïve patients from Mwanza, Tanzania (mean age 35.4 years). Twenty patients were aged <25 years and 68 patients were aged 25–63 years. The frequency of HIVDR in the study population was 14.8% (95%; CI 0.072–0.223) and independent of NVP-resistance induced by prevention of mother-to-child transmission programs. Patients >25 years had a significantly higher HIVDR frequency than younger patients (19.1%; 95% CI 0.095–0.28) versus 0%, Pu200a=u200a0.0344). In 2 out of the 16 patients with HIVDR we found traces of antiretrovirals (ARVs) in plasma. Conclusions ART-naïve patients aged over 25 years exhibited significantly higher HIVDR than younger patients. Detection of traces of ARVs in individuals with HIVDR suggests that besides transmission, undisclosed misuse of ARVs may constitute a significant factor in the generation of the observed high HIVDR rate. The current WHO tHIVDR survey that is solely focused on the transmission of HIVDR and that excludes patients over 25 years of age may therefore result in substantial underestimation of the prevalence of HIVDR in the therapy-naïve population. Similar studies should be performed also in other areas to test whether the so far reported optimistic picture of low HIVDR prevalence in young individuals is really representative for the rest of the ART-naïve HIV-infected population.

Prevalence of hepatitis B virus infection among health care workers in a tertiary hospital in Tanzania

BackgroundSub-Saharan Africa has a high prevalence of hepatitis B virus (HBV) infections. Health care workers (HCWs) are at high risk of contracting HBV infection through their occupation. Vaccination of HCWs against HBV is standard practice in many countries, but is often not implemented in resource-poor settings. We aimed with this cross-sectional study to determine HBV prevalence, HCW vaccination status, and the risk factors for HCWs contracting HBV infection in Tanzania.MethodsWe enrolled 600 HCWs from a tertiary Tanzanian hospital. Their demographics, medical histories, HBV vaccination details and risk factors for contracting blood-borne infections were collected using a standardized questionnaire. Serum samples were tested for HBV and hepatitis C virus (HCV) markers by ELISA techniques, PCR and an anti-HBs rapid test. HCWs were divided in two subgroups: those at risk of contracting HBV (rHCW 79.2xa0%) via exposure to potentially infectious materials, and those considered not at risk of contracting HBV (nrHCW, 20.8xa0%).ResultsThe overall prevalence of chronic HBV infection (HBsAg+, anti-HBc+, anti-HBs-) was 7.0xa0% (42/598). Chronic HBV infection was found in 7.4xa0% of rHCW versus 5.6xa0% of nrHCW (p-valueu2009=u20090.484). HCWs susceptible to HBV (HBsAg-, anti-HBc-, anti-HBs-) comprised 31.3xa0%. HBV immunity achieved either by healed HBV infection (HBsAg-, anti-HBc+, anti-HBs+) or by vaccination (HBsAg-, anti-HBc-, anti-HBs+) comprised 36.5xa0% and 20.2xa0%, respectively. 4.8xa0% of participants had indeterminate results (HBsAg-, anti-HBc+, anti-HBc-IgM-, anti-HBs-). Only 77.1xa0% of HCWs who received a full vaccination course had an anti-HBs titer >10xa0ml/U. An anti-HBs point-of-care test was 80.7xa0% sensitive and 96.9xa0% specific. There was a significantly higher risk for contracting HBV (anti-HBc+) among those HCW at occupational risk (rHCW) of older age (odds ratios (OR) in rHCW 3.297, pu2009<u20090.0001 vs. nrHCW 1.385, pu2009=u20090.606) and among those HCW being employed more than 11xa0years (OR 2.51, pu2009<u20090.0001***). HCV prevalence was low (HCV antibodies 1.2xa0% and HCV-RNA 0.3xa0%).ConclusionsChronic HBV infection is common among Tanzanian HCWs. One third of HCWs were susceptible to HBV infection, highlighting the need for vaccination. Due to high prevalence of naturally acquired immunity against HBV pre-testing might be a useful tool to identify susceptible individuals.

Plasma concentrations of efavirenz and nevirapine among HIV-infected patients with immunological failure attending a tertiary hospital in North-western Tanzania.

Background Sub-therapeutic and supra-therapeutic plasma concentrations of antriretrovirals are the significant causes of treatment failure and toxicity respectively among HIV-infected patients. We conducted this study to determine the pattern of efavirenz and nevirapine plasma drug concentrations among adult HIV-infected patients with immunological failure attending at a tertiary hospital in North-western Tanzania. Materials and Methods A cross-sectional study was conducted among adult HIV-infected patients with immunological failure who have been on either efavirenz or nevirapine based antiretroviral regimen for more than 6 months. Patients were serially enrolled through routine Care and Treatment Clinic (CTC) activities. Plasma drug concentrations for efavirenz and nevirapine were determined by high performance liquid chromatography (HPLC) and Gas Chromatography (GC) respectively. Demographic, clinical and laboratory data such as viral load and CD4 counts were collected. Data analysis was done using STATA 12. Results Of the 152 patients with immunological failure enrolled, the sub-therapeutic, therapeutic and supra-therapeutic plasma antiretroviral drug concentrations were found in 43/152 (28.3%), 76/152 (50.0%) and 33/152 (21.7%) respectively. Half of the patients were outside therapeutic window with either sub-therapeutic or supra-therapeutic plasma ARV drug concentrations. There was a significant difference in distribution of ARV adherence (p-value<0.001), NRTI backbone (p-valueu200a=u200a0.039), HIV stage (p-valueu200a=u200a0.026) and viral load (p-valueu200a=u200a0.007) within sub-therapeutic, therapeutic and supra-therapeutic ARV plasma drug concentrations. Conclusion There is a wide inter-individual variability of plasma ARV concentrations among HIV patients with immunological failure, with a large proportion of patients being outside therapeutic window. This variability is significant based on ARV adherence, NRTI backbone, viral load and HIV stage. Routine therapeutic drug monitoring (TDM) could assist identifying these patients early and making timely correction to avoid virological failure, poor immunological outcome and prevent associated drug toxicities. Nonetheless, ARV adherence should be strictly emphasized on HIV patients with immunological failure.

HIV patients treated with low-dose prednisolone exhibit lower immune activation than untreated patients

BackgroundHIV-associated general immune activation is a strong predictor for HIV disease progression, suggesting that chronic immune activation may drive HIV pathogenesis. Consequently, immunomodulating agents may decelerate HIV disease progression.MethodsIn an observational study, we determined immune activation in HIV patients receiving low-dose (5 mg/day) prednisolone with or without highly-active antiretroviral therapy (HAART) compared to patients without prednisolone treatment. Lymphocyte activation was determined by flow cytometry detecting expression of CD38 on CD8(+) T cells. The monocyte activation markers sCD14 and LPS binding protein (LBP) as well as inflammation markers soluble urokinase plasminogen activated receptor (suPAR) and sCD40L were determined from plasma by ELISA.ResultsCD38-expression on CD8+ T lymphocytes was significantly lower in prednisolone-treated patients compared to untreated patients (median 55.40% [percentile range 48.76-67.70] versus 73.34% [65.21-78.92], p = 0.0011, Mann-Whitney test). Similarly, we detected lower levels of sCD14 (3.6 μg/ml [2.78-5.12] vs. 6.11 μg/ml [4.58-7.70]; p = 0.0048), LBP (2.18 ng/ml [1.59-2.87] vs. 3.45 ng/ml [1.84-5.03]; p = 0.0386), suPAR antigen (2.17 μg/ml [1.65-2.81] vs. 2.56 μg/ml [2.24-4.26]; p = 0.0351) and a trend towards lower levels of sCD40L (2.70 pg/ml [1.90-4.00] vs. 3.60 pg/ml [2.95-5.30]; p = 0.0782). Viral load in both groups was similar (0.8 × 105 ng/ml [0.2-42.4 × 105] vs. 1.1 × 105 [0.5-12.2 × 105]; p = 0.3806). No effects attributable to prednisolone were observed when patients receiving HAART in combination with prednisolone were compared to patients who received HAART alone.ConclusionsPatients treated with low-dose prednisolone display significantly lower general immune activation than untreated patients. Further longitudinal studies are required to assess whether treatment with low-dose prednisolone translates into differences in HIV disease progression.

Effects of Prednisolone on Disease Progression in Antiretroviral-Untreated HIV Infection: A 2-Year Randomized, Double-Blind Placebo-Controlled Clinical Trial.

Background HIV-disease progression correlates with immune activation. Here we investigated whether corticosteroid treatment can attenuate HIV disease progression in antiretroviral-untreated patients. Methods Double-blind, placebo-controlled randomized clinical trial including 326 HIV-patients in a resource-limited setting in Tanzania (clinicaltrials.gov NCT01299948). Inclusion criteria were a CD4 count above 300 cells/μl, the absence of AIDS-defining symptoms and an ART-naïve therapy status. Study participants received 5 mg prednisolone per day or placebo for 2 years. Primary endpoint was time to progression to an AIDS-defining condition or to a CD4-count below 200 cells/μl. Results No significant change in progression towards the primary endpoint was observed in the intent-to-treat (ITT) analysis (19 cases with prednisolone versus 28 cases with placebo, p = 0.1407). In a per-protocol (PP)-analysis, 13 versus 24 study participants progressed to the primary study endpoint (p = 0.0741). Secondary endpoints: Prednisolone-treatment decreased immune activation (sCD14, suPAR, CD38/HLA-DR/CD8+) and increased CD4-counts (+77.42 ± 5.70 cells/μl compared to -37.42 ± 10.77 cells/μl under placebo, p < 0.0001). Treatment with prednisolone was associated with a 3.2-fold increase in HIV viral load (p < 0.0001). In a post-hoc analysis stratifying for sex, females treated with prednisolone progressed significantly slower to the primary study endpoint than females treated with placebo (ITT-analysis: 11 versus 21 cases, p = 0.0567; PP-analysis: 5 versus 18 cases, p = 0.0051): No changes in disease progression were observed in men. Conclusions This study could not detect any significant effects of prednisolone on disease progression in antiretroviral-untreated HIV infection within the intent-to-treat population. However, significant effects were observed on CD4 counts, immune activation and HIV viral load. This study contributes to a better understanding of the role of immune activation in the pathogenesis of HIV infection. Trial Registration ClinicalTrials.gov NCT01299948

Variability of high risk HPV genotypes among HIV infected women in Mwanza, Tanzania- the need for evaluation of current vaccine effectiveness in developing countries.

BackgroundHigh risk (HR) human papilloma Virus (HPV) genotypes have been associated with cervical cancer. In Tanzania there is a limited data on the epidemiology of HPV and genotypes distribution among HIV infected women. Here we document varieties of HPV genotypes associated with cervical squamous intraepithelial lesions (SIL) among HIV- infected women at Bugando Medical Centre, Mwanza-Tanzania.MethodsA cross sectional hospital based study involving HIV infected women was conducted between August and October, 2014. Exfoliated cells from ectocervix and endocervix were collected using cytobrush. HPV genotypes were detected using polymerase chain reaction (PCR) followed by sequencing using specific primers targeting broad range of HPV types. Cytology was done to establish squamous intraepithelial lesions. Log binomial regression analysis was done to establish risk ratios (RR) associated with HPV infection using STATA version 11.ResultsA total of 255 HIV infected women with mean age 39.2u2009±u20099.1xa0years were enrolled in the study. HPV DNA was detected in 138/255 (54.1xa0%, 95xa0% CI: 47-60) of HIV infected women. Twenty six genotypes were detected in various combinations; of these 17(65.3xa0%) were of HR genotypes. HR genotypes were detected in 124(48.6xa0%) of HIV infected women. Common HR genotypes detected were HPV-52(26), HPV-58(21), HPV-35(20) and HPV-16(14). The risk of being HPV positive was significantly higher among women with CD4 counts <100 (RR: 1.20, 95xa0% CI: 1.05-1.35, Pu2009=u20090.006) and women with SIL (RR: 1.37, 95xa0% CI: 1.11-1.68, Pu2009=u20090.005)ConclusionSignificant proportion of HIV infected women with low CD4 counts have various grades of cervical SIL associated with varieties of uncommon HR genotypes. There is a need to evaluate the effectiveness of the current vaccine in preventing cervical cancer in developing countries where HIV is endemic.

Comparison of sensitivity and specificity of three diagnostic tests to detect Schistosoma mansoni infections in school children in Mwanza region, Tanzania

Background Schistosomiasis remains one of the most prevalent parasitic infections in the world and has significant economic and public health consequences, particularly in poor communities. Reliable and accurate diagnosis plays a key role in surveillance, prevention and control of schistosomiasis. Currently, the microscopic Kato Katz (KK) stool thick smear technique is the most commonly used method to diagnose Schistosoma mansoni infections in epidemiological surveys. It is well-known that the sensitivity of this parasitological method decreases when infection intensities are moderate to low, however. The urine-based Point-of Care Circulating Cathodic Antigen (POC-CCA) test has been extensively evaluated as a further diagnostic tool. Several studies have shown that the POC-CCA test is more sensitive but less specific than the KK method. However, to clarify the meaning of inconsistent results between KK and POC-CCA tests in clinical routine, this study compares the accuracy of microscopy and POC-CCA versus real-time polymerase chain reaction (real-time PCR) results of urine and faecal samples from African school children participants. Methodology This was a school-based cross-sectional study conducted in 2015 among 305 school children aged 7–16 years from two primary schools located in Ilemela and Magu Districts, north-western Tanzania. Single stool and urine samples were collected from each participant and examined for the presence of Schistosoma mansoni eggs, parasite antigen, and parasite DNA using KK thick smears, POC-CCA tests, and real-time PCR, respectively. Principal findings The prevalence of S. mansoni infection, calculated by KK was 85.2%, by real-time PCR 92.9% and by POC-CCA 94.9%. In comparison to KK, the POC-CCA and real-time PCR tests had sensitivities of 89.7% and 99.5% and specificities of 22.73% and 29.55%, respectively. However, due to the known limitations of the KK assay, we also used latent class analysis (LCA) that included POC-CCA, KK, and schistosome-specific real-time PCR results to determine their sensitivities and specificities. The POC-CCA test had the highest sensitivity (99.5%) and a specificity of 63.4% by LCA and the real-time PCR test had a sensitivity of 98.7% and the highest specificity (81.2%). Conclusion In moderate and high prevalence areas, the POC-CCA cassette test is more sensitive than the KK method and can be used for screening and geographical mapping of S. mansoni infections. Real-time PCR is highly sensitive and also shows the highest specificity among the 3 investigated diagnostic procedures. It can offer added value in diagnosing schistosomiasis.

Prevalence of pretreatment HIV drug resistance in Mwanza, Tanzania

BackgroundnIn a 2008-10 study, we found a pretreatment HIV drug resistance (PDR) prevalence of 18.2% in patients at Bugando Medical Centre (BMC) in Mwanza, Tanzania.nnnObjectivesnTo determine the prevalence of PDR and transmitted HIV drug resistance (TDR) in patients visiting the BMC from 2013 to 2015.nnnMethodsnAdult outpatients were sequentially enrolled into two groups, separated by whether they were initiating ART. Previous exposure to antiretroviral drugs, except for prevention of mother-to-child transmission, was an exclusion criterion. HIV pol sequences were analysed according to WHO guidelines for surveillance of PDR and TDR.nnnResultsnTwo hundred and thirty-five sequences were analysed (138 ART initiators, 97 non-initiators). The prevalence of PDR was 4.7% (95% CI 2.6%-8.2%) overall, 3.1% (95% CI 1.1%-8.7%) for non-initiators and 5.8% (95% CI 3.0%-11.0%) for ART initiators. PDR to NNRTIs and nucleoside or nucelotide reverse transcriptase inhibitors was found in 3.0% (95% CI 1.5%-6.0%) and 1.7% (95% CI 0.7%-4.3%) of patients, respectively. Resistance to PIs was not observed. The prevalence of TDR was 6.0% (95% CI 3.6%-9.8%).nnnConclusionsnPrevalence of PDR significantly decreased compared with 2008-10 and was below the WHO-defined threshold for triggering a public health response. National and systematic surveillance is needed to inform Tanzanias public health strategy.

Prevalence and factors associated with Mycobacteremia and mortality among febrile HIV infected patients in Mwanza, Tanzania

OBJECTIVESnThis study investigated the prevalence and factors associated with mycobacteremia and mortality among febrile HIV infected patients in developing countries.nnnMETHODSnA hospital based cross-sectional study was conducted among febrile HIV patients admitted at Bugando Medical centre and Sekou Toure hospital between November 2016 and March 2017. Blood culture was done on BACTEC Myco/F Lytic bottles. Clinical and demographic data were collected using a pre-tested data collection tool.nnnRESULTSnA total of 154 patients with the mean age of 41.5±12.2 were enrolled. Females formed the majority, 93 (60%) of the study participants. The prevalence of Mycobacteremia was 3.3% while that of other bacteria was 8.4%. Age (p=0.03), recent HIV diagnosis (p=0.005), not taking HAART (p=0.031) and low CD4+ count (p=0.002) were significantly associated with Mycobacteremia. Factors significantly associated with 14-day in-hospital mortality were advanced HIV infection (p<0.001), poor ART adherence (p<0.001), low CD4+ (p=0.0002) and Mycobacteremia (p=0.007).nnnCONCLUSIONnThe prevalence of Mycobacteremia was low; however, it was significantly associated with mortality. Mycobacteremia should be suspected in high risk febrile HIV infected individuals followed by early appropriate treatment in order to reduce associated morbidity and mortality.

The magnitude of antibiotic resistance to Helicobacter pylori in Africa and identified mutations which confer resistance to antibiotics: systematic review and meta-analysis

BackgroundWorldwide Helicobacter pylori (H.pylori) treatment is of great challenge due to increased antibiotic resistance. The burden of H. pylori antibiotic resistance in Africa is high with unclear information regarding the real magnitude. This systematic review and meta-analysis was conducted to investigate the magnitude of H.pylori antibiotic resistance in Africa to gain insight of the extent of the problem among H.pylori naïve treatment patients.MethodThe search was performed in the academic databases, Embase, PubMed, Web of Science and Africa Wide Information. ProQuest Dissertation and Theses, Scopus, Ethos, Africa Index Medicus (WHO), BioMed Central Proceedings, BASE, British Library, Open grey, Library of Congress and the New York Academy of Grey Literature Report were additionally searched for grey literature. Published articles from Africa on H.pylori antibiotic resistance between 1986 and June 2017 were systematically reviewed to estimate the H. pylori extent of resistance to macrolides, quinolones, amoxicillin, tetracycline and metronidazole.ResultsIn 26 articles a total of 2085 isolates were tested for metronidazole, 1530 for amoxicillin, 1277 for tetracycline, 1752 for clarithromycin and 823 for quinolones.The overall pooled proportion of H.pylori resistance to quinolones, clarithromycin, tetracycline, metronidazole and amoxicillin were: (17.4%, 95%CI 12.8 - 21.9), (29.2%, 95%CI:26.7-31.8), (48.7%, 95%CI: 44.5-52.9), (75.8%, 95% CI: 74.1-.77.4) and (72.6%, 95% CI: 68.6-76.6), respectively. The commonest mutation detected were A2143G (49/97) for clarithromycin, RdxA (41/56) for metronidazole and D87I (16/40) for quinolones.ConclusionPrevalence of metronidazole, clarithromycin, and amoxicillin resistance is high in developing world including Africa. This could impair the first line triple therapy of the H.pylori infection. There is a need of conducting surveillance of H.pylori susceptibility pattern in Africa for dual and triple resistance which can be used for the empirical treatment.