Per Kallestrup

Schistosomiasis and HIV-1 Infection in Rural Zimbabwe: Effect of Treatment of Schistosomiasis on CD4 Cell Count and Plasma HIV-1 RNA Load

To determine whether treatment of schistosomiasis has an effect on the course of human immunodeficiency virus type 1 (HIV-1) infection, individuals with schistosomiasis and with or without HIV-1 infection were randomized to receive praziquantel treatment at inclusion or after a delay of 3 months; 287 participants were included in the study, and 227 (79%) were followed up. Among the 130 participants who were coinfected, those who received early treatment (n=64) had a significantly lower increase in plasma HIV-1 RNA load than did those who received delayed treatment (n=66) (P<.05); this difference was associated with no change in plasma HIV-1 RNA load in the early intervention group (P=.99) and an increase in plasma HIV-1 RNA load in the delayed intervention group (P<.01). Among the 227 participants who were followed up, those who received early treatment (n=105) had an increase in CD4 cell count, whereas those who received delayed treatment (n=122) did not (P<.05); this effect did not differ between participants when stratified by HIV-1 infection status (P=.17). The present study suggests that treatment of schistosomiasis can reduce the rate of viral replication and increase CD4 cell count in the coinfected host.

Schistosomiasis and HIV-1 Infection in Rural Zimbabwe: Implications of Coinfection for Excretion of Eggs

BACKGROUND Stunted development and reduced fecundity of Schistosoma parasites in immunodeficient mice and the impaired ability of human immunodeficiency virus 1 (HIV-1)-infected humans to excrete schistosome eggs have been described. This study explores the effect that HIV-1-associated immunodeficiency has on the excretion of schistosome eggs in a large cohort of coinfected individuals. METHODS In a cross-sectional survey, urine and stool samples were obtained from and HIV-1 status was determined for 1545 individuals. More extensive data, including quantitative measures of intensity of infection in schistosomiasis and immunodeficiency, were collected in the Mupfure schistosomiasis and HIV longitudinal cohort, composed of 379 participants of whom 154 were coinfected with HIV-1 and Schistosoma parasites. RESULTS In the cross-sectional survey, the overall prevalence of schistosomiasis was 43.4%, and 26.3% of the participants were infected with HIV-1. Schistosome infections were due to Schistosoma haematobium in 63.6% of cases, S. mansoni in 18.1% of cases, and dual infections in 18.4% of cases. Intensities of Schistosoma infections, measured by the number of eggs excreted and by the level of circulating anodic antigens, did not differ between HIV-1-negative and HIV-1-positive participants coinfected with S. haematobium, S. mansoni, or both. CD4 cell counts were significantly lower in HIV-1-positive participants and in S. mansoni-infected HIV-1-negative participants than in other participants. CONCLUSION The present study suggests that adult HIV-1-related immunodeficiency does not impair the ability to excrete eggs in low-intensity infection with S. haematobium, S. mansoni, or both and that infection with HIV-1 may not have major implications for diagnosis and surveillance of schistosomiasis.

Prevalence of Hypertension in Member Countries of South Asian Association for Regional Cooperation (SAARC): Systematic Review and Meta-Analysis

AbstractHypertension is a leading attributable risk factor for mortality in South Asia. However, a systematic review on prevalence and risk factors for hypertension in the region of the South Asian Association for Regional Cooperation (SAARC) has not carried out before.The study was conducted according to the Meta-Analysis of Observational Studies in Epidemiology Guideline. A literature search was performed with a combination of medical subject headings terms, “hypertension” and “Epidemiology/EP”. The search was supplemented by cross-references. Thirty-three publications that met the inclusion criteria were included in the synthesis and meta-analyses. Hypertension is defined when an individual had a systolic blood pressure (SBP) ≥140 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg, was taking antihypertensive drugs, or had previously been diagnosed as hypertensive by health care professionals. Prehypertension is defined as SBP 120–139 mm Hg and DBP 80–89 mm Hg.The overall prevalence of hypertension and prehypertension from the studies was found to be 27% and 29.6%, respectively. Hypertension varied between the studies, which ranged from 13.6% to 47.9% and was found to be higher in the studies conducted in urban areas than in rural areas. The prevalence of hypertension from the latest studies was: Bangladesh: 17.9%; Bhutan: 23.9%; India: 31.4%; Maldives: 31.5%; Nepal: 33.8%; Pakistan: 25%; and Sri Lanka: 20.9%. Eight out of 19 studies with information about prevalence of hypertension in both sexes showed that the prevalence was higher among women than men. Meta-analyses showed that sex (men: odds ratio [OR] 1.19; 95% confidence interval [CI]: 1.02, 1.37), obesity (OR 2.33; 95% CI: 1.87, 2.78), and central obesity (OR 2.16; 95% CI: 1.37, 2.95) were associated with hypertension.Our study found a variable prevalence of hypertension across SAARC countries, with a number of countries with blood pressure above the global average. We also noted that studies are not consistent in their data collection about hypertension and related modifiable risk factors.

Reduced mortality and CD4 cell loss among carriers of the interleukin-10 -1082G allele in a Zimbabwean cohort of HIV-1-infected adults.

Objectives:To evaluate the effect on HIV progression of single nucleotide polymorphisms in promoters of the genes for tumour necrosis factor (TNF)-α and interleukin (IL)-10 and known to influence cytokine production. Methods:Survival was documented for 4.3 years after baseline for 198 HIV-1-infected and 180 HIV-uninfected individuals from the Mupfure Schistosomiasis and HIV Cohort in rural Zimbabwe. Polymorphisms determined were −592C>A and −1082A>G for IL-10 and −238G>A and −308G>A for TNF-α. CD4 cell counts, plasma HIV RNA, soluble TNF receptor II (sTNF-rII), IL-8 and IL-10 were also measured. Results:Mortality was lower in carriers of the IL-10 −1082G high-producer allele (hazard ratio, 0.47; P < 0.01). CD4 cell count decrease in participants reporting for the follow-up at 3 years was attenuated in carriers of this allele (P < 0.01). In univariate analysis, plasma IL-10, IL-8, and sTNF-rII correlated negatively with CD4 cell count, positively with HIV RNA, and higher levels predicted mortality. In multivariate analysis only sTNF-rII was an independent predictor of HIV progression markers and mortality. Indeed, sTNF-rII predicted mortality (P < 0.01) at a level of significance comparable to HIV RNA (P < 0.01) and CD4 cell count (P < 0.05). Conclusions:In carriers of IL-10 −1082G, an allele linked to increased IL-10 production, survival was doubled and CD4 cell decrease was attenuated compared with noncarriers. Only sTNF-rII and not plasma IL-10 was an independent predictor of HIV progression markers and mortality. This study supports immune activation as a driving force in HIV pathogenesis and indicates a protective role of IL-10 −1082G that should be evaluated in other cohorts.

Predictors of mortality in a cohort of HIV-1-infected adults in rural Africa.

Background:CD4 cell count and plasma HIV RNA level are used to monitor HIV-infected patients in high-income countries, but the applicability in an African context with frequent concomitant infections has only been studied sparsely. Moreover, alternative inexpensive markers are needed in the attempts to roll out antiretroviral treatment in the region. We explored the prognostic strengths of classic and alternative progression markers in this study set in rural Zimbabwe. Methods:We followed 196 treatment-naive HIV-1-infected patients from the Mupfure Schistosomiasis and HIV Cohort, Zimbabwe. CD4 cell count, HIV RNA level, hemoglobin (HB), total lymphocyte count (TLC), body mass index, clinical staging (Centers for Disease Control and Prevention [CDC] classification), and self-reported level of function (Karnofsky Performance Scale score) were assessed at baseline; participants were followed until death or last follow-up (3-4.3 years). Results:All parameters except TLC predicted survival in univariate Cox models. HIV RNA level (P = 0.001), HB (P = 0.018), CD4 cell count (P = 0.047), and CDC category C (P = 0.007) remained significant in multivariate analysis. Conclusions:We found HIV RNA level and CD4 cell count to predict mortality with prognostic capabilities similar to findings from high-income countries. HB and clinical staging were strong independent predictors and might be considered candidates for alternative HIV progression markers.

Schistosomiasis and HIV in Rural Zimbabwe: Efficacy of Treatment of Schistosomiasis in Individuals with HIV Coinfection

BACKGROUND There is evidence from experimental models that the praziquantel-induced clearance of schistosomiasis is dependent on the hosts immune response. Consequently, human immunodeficiency virus (HIV)-related immunodeficiency may impair the effect of praziquantel treatment. METHODS In a prospective cohort study, schistosome-infected subjects who were or were not coinfected with HIV were treated with praziquantel and followed up 3, 6, and 12 months after treatment. Quantitative measures of intensity of schistosomiasis (egg counts and levels of circulating anodic antigen in serum) and immunodeficiency (CD4+ cell counts and viral loads) were collected. RESULTS Cure rates based on egg counts 3 months after treatment were satisfactory and were similar for HIV-positive individuals (cure rate, 86%) and HIV-negative individuals (cure rate, 85%); the magnitude of decrease in egg count was equal. Cure rates based on circulating anodic antigen levels were much lower than cure rates based on egg counts, with HIV-positive individuals experiencing significantly less clearance of schistosomiasis (cure rate, 31%) than HIV-negative individuals (cure rate, 52%), whereas the magnitude of decrease in circulating anodic antigen was also lower among HIV-positive individuals (P < .01). CONCLUSION The effect of praziquantel may be limited to affecting the fecundity of adult schistosomes in the immunocompromised host, thus reducing egg excretion while leaving schistosomes metabolically active, as shown by the fact that levels of antigen production are maintained. Special guidelines for treatment of schistosomiasis in HIV-coinfected individuals may need to be developed.

Longitudinal Analysis of CCR5 and CXCR4 Usage in a Cohort of Antiretroviral Therapy-Naïve Subjects with Progressive HIV-1 Subtype C Infection

HIV-1 subtype C (C-HIV) is responsible for most HIV-1 cases worldwide. Although the pathogenesis of C-HIV is thought to predominantly involve CCR5-restricted (R5) strains, we do not have a firm understanding of how frequently CXCR4-using (X4 and R5X4) variants emerge in subjects with progressive C-HIV infection. Nor do we completely understand the molecular determinants of coreceptor switching by C-HIV variants. Here, we characterized a panel of HIV-1 envelope glycoproteins (Envs) (n = 300) cloned sequentially from plasma of 21 antiretroviral therapy (ART)-naïve subjects who experienced progression from chronic to advanced stages of C-HIV infection, and show that CXCR4-using C-HIV variants emerged in only one individual. Mutagenesis studies and structural models suggest that the evolution of R5 to X4 variants in this subject principally involved acquisition of an “Ile-Gly” insertion in the gp120 V3 loop and replacement of the V3 “Gly-Pro-Gly” crown with a “Gly-Arg-Gly” motif, but that the accumulation of additional gp120 “scaffold” mutations was required for these V3 loop changes to confer functional effects. In this context, either of the V3 loop changes could confer possible transitional R5X4 phenotypes, but when present together they completely abolished CCR5 usage and conferred the X4 phenotype. Our results show that the emergence of CXCR4-using strains is rare in this cohort of untreated individuals with advanced C-HIV infection. In the subject where X4 variants did emerge, alterations in the gp120 V3 loop were necessary but not sufficient to confer CXCR4 usage.

Burgeoning burden of non-communicable diseases in Nepal: a scoping review.

In the last decades, prevalence of non-communicable diseases (NCDs) has escalated in Nepal. This study reviews existing evidence on the burden of non-communicable diseases in Nepal using the framework developed by Arksey and O’Malley for scoping reviews. A total of 110 articles were identified from database searches, and four from additional searches. The titles and abstracts were reviewed using predetermined screening criteria. We limited our search to existing literature in English language and included all studies regardless of year of study. Both observational and interventional studies were included. Studies conducted outside Nepal and studies not reporting prevalence of NCDs were excluded. Additionally, we searched reference lists of included publications. All previous reports of Step Wise Surveillance to NCDs (STEPS Surveys) were included in the review. Finally, a total of 60 articles were included in this review. Limited studies on population-based prevalence of mental illness, chronic respiratory diseases, cardiovascular diseases, and road traffic accidents were found. There were limitations in the studies related to generalizability due to small sample sizes, non-random sampling and lack of studies from certain region of country. Nevertheless, high prevalence of hypertension and diabetes was found. Similarly, hospital-based studies reported high burden of cardiovascular diseases among outpatient contacts. Population-based cancer registries do not exist in Nepal. However, existing studies report 8,000-10,000 cancer deaths annually in Nepal. The most common cancer site in males was the lung, followed by the oral cavity and gastric, while the first three in females were cervix uteri, breast and lung. Prevalence of psychiatric morbidity was also high. Despite alarming burden of NCDs, the country’s response is weak. Nepal needs to build non-communicable disease programmes with focus on disease prevention and management as well as awareness activities in urban and rural settings at community level.

Non-adherence to anti-hypertensive medication in low- and middle-income countries: a systematic review and meta-analysis of 92443 subjects

Hypertension is a rising global burden, and low- and middle-income countries account for 80% of deaths due to complications of hypertension. Hypertension can be controlled by adhering to anti-hypertensive medication. However, non-adherence is an increasing challenge. This review aims to systematically evaluate non-adherence to anti-hypertensive medication among adults in low- and middle-income countries and explore factors affecting non-adherence to anti-hypertensive medication. We performed a systematic search for studies published between 1 January 2000 and 31 August 2015. A selection process was performed for data extraction with a combination of Medical Subject Headings terms: ‘hypertension’ and ‘adherence’. Further search criteria were: language (‘english’), species (‘humans’), and low- and middle-income countries. A total of 22 studies met the inclusion criteria. The pooled percentage of non-adherence when using the eight-item Morisky Medication Adherence Scale (MMAS) was 63.35% (confidence of interval (CI): 38.78–87.91) and 25.45% (CI:17.23–33.76) when using the 80 and 90% cut-off scales. The factors were classified into the five dimensions of adherence defined by the World Health Organization, and the majority of the studies reported factors from the dimension ‘social and economic factors’. This systematic review demonstrated considerable variation of non-adherence to anti-hypertensive medication in low- and middle-income countries depending on the methods used to estimate non-adherence. The results showed a high non-adherence when the MMAS eight-item scale was used and low when the 80 and 90% cut-off scales were used. The majority of factors affecting non-adherence to anti-hypertensive medication fell within the World Health Organization defined dimension ‘social and economic factors’.

Prevalence of type 2 diabetes in Nepal: a systematic review and meta-analysis from 2000 to 2014

Background Understanding the prevalence of type 2 diabetes in Nepal can help in planning for health services and recognising risk factors. This review aims to systematically identify and collate studies describing the prevalence of type 2 diabetes, to summarise the findings, and to explore selected factors that may influence prevalence estimates. Design This systematic review was conducted in adherence to the MOOSE Guidelines for Meta-Analysis and Systematic Reviews of Observational Studies. Medical Literature Analysis and Retrieval System (MEDLINE) database from 1 January 2000 to 31 December 2014 was searched for the prevalence of type 2 diabetes among Nepalese populations with a combination of search terms. We exploded the search terms to include all possible synonyms and spellings obtained in the search strategy. Additionally, we performed a manual search for other articles and references of published articles. Results We found 65 articles; 10 studies fulfilled the inclusion criteria and were included in the analyses. These 10 studies comprised a total of 30,218 subjects. The sample size ranged from 489 to 14,009. All the studies used participants older than age 15, of whom 41.5% were male and 58.5% female. All the studies were cross-sectional and two were hospital-based. Prevalence of type 2 diabetes ranged from a minimum of 1.4% to a maximum of 19.0% and pooled prevalence of type 2 diabetes was 8.4% (95% CI: 6.2–10.5%). Prevalence of type 2 diabetes in urban and rural populations was 8.1% (95% CI: 7.3–8.9%) and 1.0% (95% CI: 0.7–1.3%), respectively. Conclusions This is, to our knowledge, the first study to systematically evaluate the literature of prevalence of type 2 diabetes in Nepal. Results showed that type 2 diabetes is currently a high-burden disease in Nepal, suggesting a possible area to deliberately expand preventive interventions as well as efforts to control the disease.