Open label randomized comparison of dihydroartemisinin–piperaquine and artesunate–amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in central Vietnam

Objective  Artesunate–amodiaquine (AAQ) is efficacious for the treatment of uncomplicated Plasmodium falciparum malaria in Africa, but little is known about its efficacy in Southeast Asia. We compared the efficacy of dihydroartemisinin–piperaquine (DHP) and AAQ against falciparum malaria in central Vietnam.
Methods  Open, randomized clinical trial of 116 patients (36 children aged 6–14 years, 80 adults aged 15–60 years) were randomly allocated a 3-day course of either DHP (∼2.3 mg/kg dihydroartemisinin plus ∼18.5 mg/kg of piperaquine per day) or AAQ (∼4.4 mg/kg of artesunate plus ∼10.6 mg/kg of amodiaquine per day). The follow-up period was 42 days.
Results  The two drug combinations were well tolerated by all age groups with no obvious drug associated adverse events. Of the patients who completed 42 days of follow-up, 49 were on DHP (15 children, 34 adults) and 49 were on AAQ (14 children, 35 adults). The 42 day cure rates adjusted for reinfection identified by PCR genotyping for the two groups were similar [100% (49/49) and 98% (48/49) for DHP and AAQ, respectively]. With fewer reinfections, DHP appears to possess greater post-treatment prophylactic activity than AAQ.
Conclusion  AAQ, an inexpensive artemisinin-based combination, could be an additional option to DHP for the treatment of multidrug-resistant falciparum malaria in Vietnam.     

Influence of consecutive-day blood sampling on polymerase chain reaction-adjusted parasitological cure rates in an antimalarial-drug trial conducted in Tanzania

We assessed the influence that consecutive-day blood sampling, compared with single-day blood sampling, had on polymerase chain reaction (PCR)-adjusted parasitological cure after stepwise genotyping of merozoite surface proteins 2 (msp2) and 1 (msp1) in 106 children in Tanzania who had uncomplicated falciparum malaria treated with either sulfadoxine-pyrimethamine or artemether-lumefantrine; 78 of these children developed recurrent parasitemia during the 42-day follow-up period. Initial msp2 genotyping identified 27 and 33 recrudescences by use of single- and consecutive-day sampling, respectively; in subsequent msp1 genotyping, 17 and 21 of these episodes, respectively, were still classified as recrudescences; these results indicate a similar sensitivity of the standard single-day PCR protocol--that is, 82% (27/33) and 81% (17/21), in both genotyping steps. Interpretation of PCR-adjusted results will significantly depend on methodology.     

Molecular genotyping in a malaria treatment trial in Uganda - unexpected high rate of new infections within 2 weeks after treatment

Polymerase chain reaction (PCR) genotyping of malaria parasites in drug efficacy trials helps differentiate reinfections from recrudescences. A combination therapy trial of one (n = 115) or three (n = 117) days artesunate (1AS, 3AS 4 mg/kg/day) plus sulphadoxine-pyrimethamine (SP) vs. SP alone (n = 153) was conducted in Mbarara, a mesoendemic area of western Uganda. All paired recurrent Plasmodium falciparum parasitaemias on days 7, 14, 21 and 28 post-treatment were genotyped by PCR amplification and analysis of glutamate-rich protein (glurp) and merozoite surface proteins (msp) 1 and 2 genes to distinguish recrudescent from new infections. A total of 156 (1AS = 61, 3AS = 35, SP alone = 60) of 199 paired recurrent samples were successfully analysed and were resolved as 79 recrudescences (1AS = 32, 3AS = 8, SP = 39) and 77 as new infections (1AS = 29, 3AS = 27, SP = 21). The ratios of proportions of new to recrudescent infections were 0.2, 0.9, 1.4 and 1.9 on days 7, 14, 21 and 28, respectively (P < 0.001, chi(2) test for linear trend). Unexpected high new infection rates were observed early in follow-up on days 7 [5/26 (19.2%)] and 14 [24/51 (47.1%)]. These results impact significantly on resistance monitoring and point to the value of genotyping all recurrent infections in antimalarial trials.     

Effectiveness of chemoprophylaxis and other determinants of malaria in travellers to Kenya

Summary objective  To investigate the effectiveness of chemoprophylaxis and the determinants of malaria importation from Kenya.
method  In a population-based case-control study, 51 travellers from Bavaria diagnosed with falciparum malaria imported from Kenya (cases) and a sample of 383 healthy Bavarian travellers returning from Kenya (controls) were interviewed. Data were analysed by multiple logistic regression.
results  Mefloquine (OR = 0.055; 95% Cl 0.019-0.16) and chloroquine combined with proguanil (OR = 0.128; 95% CI 0.039-0.419) were highly protective against P. falciparum malaria, whereas other drugs were ineffective (OR = 1.225; 95% CI 0.536-2.803). Ineffective prophylaxis (10.4%) and non-prophylaxis (11.2%) were the main reasons for malaria importation. Travelling alone or with friends, male sex, and travel duration over 4 weeks could be identified as additional risk factors. The main reason for inadequate chemoprophylaxis was inappropriate medical advice (87.5%). Prophylaxis refusal occurred frequently despite correct advice (58.1%). Diagnosis was often delayed unnecessarily (27.5%).
conclusion  Malaria importation from Kenya could be reduced substantially (34%) by eliminating inappropriate medical advice.     

Performance of OptiMAL-IT® compared to microscopy, for malaria detection in Burkina Faso

Objective  To compare the performance of OptiMAL-IT^®, a rapid diagnostic test for malaria, with that of microscopy in Burkina Faso.
Method  Finger-prick blood samples of 464 children attending hospital for suspected malaria were tested for malaria by microscopy and OptiMAL-IT^®.
Results  The sensitivity and specificity of OptiMAL-IT^® were 98.7% (CI 95% = 97.6–99.8) and 96.2% (CI 95% = 94.3–98.1) respectively, with a high positive likelihood ratio (25.97).
Conclusion  OptiMAL-IT^® can be considered a good method to diagnose malaria in Burkina Faso, particularly in remote areas with little or no access to microscopy services.     

Efficacy of methylene blue monotherapy in semi‐immune adults with uncomplicated falciparum malaria: a controlled trial in Burkina Faso

Objective To assess the efficacy of methylene blue (MB) monotherapy in semi‐immune adults with uncomplicated malaria in Burkina Faso. Methods In an open‐label controlled phase II study with 60 semi‐immune adults with uncomplicated falciparum malaria in Nouna, north‐western Burkina Faso, MB monotherapy (390 mg twice daily) was given sequentially to groups of 20 adults for 7 days (MB7), 5 days (MB5) and 3 days (MB3), respectively. The primary outcome was the rate of adequate clinical and parasitological response (ACPR) on day 28 of follow‐up. Results Of the study population, 27/58 (47%) and 5/51 (10%) patients still had parasites on days 2 and 3, respectively, of follow‐up resulting in 9/58 (16%) early treatment failures. By day 14, no recrudescence was observed but in 4/19 (MB5) and 2/20 (MB3) individuals by day 28. The PCR‐corrected rate of ACPR was 72%, 58% and 85% in groups 7, 5 and 3, respectively, by per protocol analysis. Self‐limiting dysuria was the most frequent adverse event. Conclusions MB acts slowly against the blood stages of P. falciparum. MB alone needs to be given for at least 7 days to be efficacious in the treatment of falciparum malaria but should be used in combination with a fast acting antimalarial.     

Hepcidin Regulation in Wild-Type and Hfe Knockout Mice in Response to Alcohol Consumption: Evidence for an Alcohol-Induced Hypoxic Response

Background /Aims:  Expression of Hamp1 , the gene encoding the iron regulatory peptide hepcidin, is inappropriately low in HFE-associated hereditary hemochromatosis and Hfe knockout mice ( Hfe ^−/− ). Since chronic alcohol consumption is also associated with disturbances in iron metabolism, we investigated the effects of alcohol consumption on hepcidin mRNA expression in Hfe ^−/− mice.
Methods:  Hfe ^−/− and C57BL/6 (wild-type) mice were pair-fed either an alcohol liquid diet or control diet for up to 8 weeks. The mRNA levels of hepcidin and ferroportin were measured at the mRNA level by RT-PCR and protein expression of hypoxia inducible factor-1 alpha (HIF-1α) was measured by western blot.
Results:  Hamp1 mRNA expression was significantly decreased and duodenal ferroportin expression was increased in alcohol-fed wild-type mice at 8 weeks. Time course experiments showed that the decrease in hepcidin mRNA was not immediate, but was significant by 4 weeks. Consistent with the genetic defect, Hamp1 mRNA was decreased and duodenal ferroportin mRNA expression was increased in Hfe ^−/− mice fed on the control diet compared with wild-type animals and alcohol further exacerbated these effects. HIF-1α protein levels were elevated in alcohol-fed wild-type animals compared with controls.
Conclusion:  Alcohol may decrease Hamp1 gene expression independently of the HFE pathway possibly via alcohol-induced hypoxia.     

双氢青蒿素-磷酸哌喹和蒿甲醚-本芴醇两种复方对海南岛无并发症恶性疟的疗效观察

目的 观察双氢青蒿素-磷酸哌喹和蒿甲醚-本芴醇两种复方抗疟药对海南岛无并发症恶性疟的治疗效果。 方法 2005-2006年在海南省5县（市）恶性疟流行区,选择1～60岁无并发症单纯恶性疟病例107例（原虫无性体密度为1 000～200 000个/μl）,病例随机分为2组,A组55例, 口服双氢青蒿素-磷酸哌喹治疗（成人总剂量8片,1次/d,疗程为3 d,首日4片）, B组52例,口服蒿甲醚-本芴醇治疗（成人总剂量24片,2次/d,早晚各服4片,疗程为3 d）。 按照WHO体内法观察标准进行治疗、观察和随访。 结果 A组55例,全部完成治疗、观察和28 d随访,平均退热时间为(22.35±13.26） h,平均原虫转阴时间为（34.99±12.28） h;B组52例中有51例完成治疗、观察和28 d随访, 平均退热时间为（20.99±11.38） h,平均原虫转阴时间为（36.45±12.60） h,两组间差异均无统计学意义（P>0.05）。28 d随访两组病例均未出现复燃。个别病例在服药后出现中枢神经系统及胃肠道反应, 如头痛、恶心、呕吐等,症状较轻,停药后即自行消失。未出现严重的不良反应。 结论 双氢青蒿素-磷酸哌喹和蒿甲醚-本芴醇两复方治疗海南岛无并发症恶性疟效果好,控制症状快,治愈率高。     

Monitoring of CD95 and CD38 expression in peripheral blood T lymphocytes during active human cytomegalovirus infection after orthotopic liver transplantation

Aim:  The aim of the present study was to quantitatively monitor the response of CD95 molecules expressed on CD3⁺ T cells (CD95⁺CD3⁺ cells) and CD38 molecules expressed on CD8⁺ T cells (CD38⁺CD8⁺ cells) to ganciclovir treatment after orthotopic liver transplant (OLT) in recipients with active human cytomegalovirus (HCMV) infection.
Methods:  Blood samples were collected from 20 liver transplanted recipients with active HCMV infection and 24 recipients without HCMV infection. CD95⁺CD3⁺ cells and CD38⁺CD8⁺ cells were quantitatively detected with QuantiBRITE bead methods by dual-color flow cytometry analysis during the post-transplantation period.
Results:  CD95⁺CD3⁺ cells and CD38⁺CD8⁺ cells were not significantly different among different ages of healthy adults ( P  > 0.05). CD95⁺CD3⁺ cells and CD38⁺CD8⁺ cells were drastically increased in the active HCMV infection group compared with that in the stable group or in the healthy group ( P  < 0.001), and then they were gradually decreased within the next several weeks after ganciclovir treatment when compared with active HCMV infection recipients ( P  < 0.001).
Conclusions:  The present study showed that CD38⁺CD8⁺ T cells can be an appropriate immunological marker for early detection and antiviral therapeutic monitoring of HCMV infection. The evaluation of CD95 molecule levels may be used routinely in clinical practice to assess the level of immunosuppression.     

Risk associated with asymptomatic parasitaemia occurring post-antimalarial treatment

Objective  Parasites may recur asymptomatically after initial clearance by antimalarial treatment. Current guidelines recommend treatment only when patients develop symptoms or at the end of follow-up. We wanted to assess prospectively the probability of becoming symptomatic and the risks of this practice.
Methods  We analysed data collected in 13 trials of uncomplicated paediatric malaria conducted in eight sub-Saharan African countries. These studies followed all cases of post-treatment asymptomatic parasitaemia until they developed symptoms or to the end of the 28-day follow-up period, at which time parasite genotypes were compared to pre-treatment isolates to distinguish between recrudescences and new infections.
Results  There were 425 asymptomatic recurrences after 2576 treatments with either chloroquine, sulfadoxine/pyrimethamine or amodiaquine, of which 225 occurred by day 14 and 200 between day 15 and day 28. By day 28, 42% developed fever (median time to fever = 5 days) and 30% remained parasitaemic but afebrile, while 23% cleared their parasites (outcome unknown in 4%). Young age, parasitaemia ≥500 parasites/μl; onset of parasitaemia after day 14, and treatment with amodiaquine were the main variables associated with higher risk of developing fever.
Conclusion  In areas of moderate to intense transmission, asymptomatic recurrences of malaria after treatment carry a substantial risk of becoming ill within a few days and should be treated as discovered. Young children are at higher risk. The higher risk carried by cases occurring in the second half of follow-up may be explained by falling residual drug levels.     

Impact of delayed introduction of sulfadoxine–pyrimethamine and arthemeter–lumefantrine on malaria epidemiology in KwaZulu-Natal, South Africa

Objective  To investigate how delayed introduction of sulfadoxine–pyrimethamine (Fansidar^®) and arthemeter–lumefantrine (Coartem^®) as first-line drugs for malaria in KwaZulu-Natal contributed to the reported epidemics of 1985–1988 and 1997–2001.
Methods  Ecological study assessing the association between malaria incidence and the emergence and degree of resistance to chloroquine from 1982 to 1988 and to sulfadoxine–pyrimethamine from 1991 to 2001, when each was the first-line malaria treatment.
Results  The relative risk for malaria infection after the level of drug resistance reached 10% was 4.5 (95% CI: 4.0–5.2) in the chloroquine period and 5.9 (95% CI: 5.7–6.1) in the sulfadoxine–pyrimethamine period. In the chloroquine period, the relative risk of death from malaria was tenfold (95% CI: 1.3–78.1) and the case fatality doubled after drug resistance had reached 10%. The risk of death during the sulfadoxine–pyrimethamine period was 10.8 (95% CI: 5.9–19.2) and case fatality 1.8 times higher after drug resistance had reached 10%, than before.
Conclusion  Malaria epidemics in KwaZulu-Natal, South Africa have been exacerbated by failing drug regimens. The establishment of sentinel sites for monitoring drug failure and the prompt adoption of guidelines based on World Health Organization standards in drug resistance should improve malaria control.     

Efficacy and limitation of bone marrow transplantation in the treatment of acute and subacute liver failure in rats

Aim:  Recent reports have shown that bone marrow cells (BMC) retain the potential to differentiate into hepatocytes. Thus, the BMC have been recognized as an attractive source for liver regenerative medicine. However, it has not been clarified whether BMC transplantation can be used to treat liver damage in vivo . In the present study, we explored whether BMC possess therapeutic potential to treat acute and/or subacute liver failure.
Methods:  Fulminant hepatic failure (FHF) was induced by 70% hepatectomy with ligation of the right lobe pedicle (24% liver mass), followed by transplantation of BMC into the spleen. Dipeptidyl peptidase IV-positive (DPPIV⁺) BMC were then transplanted into DPPIV-negative (DPPIV^-) recipients following hepatic irradiation (HIR) in which 70% of the liver was resected and the remnant liver irradiated.
Results:  There was no benefit of BMC transplantation towards survival in the FHF model. DPPIV⁺ hepatocytes appeared in the liver tissues of the DPPIV^- HIR model rats, but DPPIV⁺ hepatocytes replaced less than 13% of the recipient liver.
Conclusion:  BMC transplantation may have limitations in the treatment of fulminant or acute liver failure because they do not have sufficient time to develop into functional hepatocytes. Preparative HIR may be beneficial in help to convert the transplanted BMC into host hepatocytes, and provide a survival benefit. Although, However, the precise mechanism warrants further studies.     

Disruption of tissue-type plasminogen activator gene in mice aggravated liver fibrosis

Background and Aim:  Tissue-type plasminogen activator (tPA) is one of the major components in the matrix proteolytic network whose role in the pathogenesis of liver fibrosis remains unknown. The aim of this study is to investigate the role of tPA in carbon tetrachloride (CCl₄)-induced liver fibrosis.
Methods:  Wild-type and tPA knockout mice (8 mice per group) were injected interperitoneumly with 25% CCl₄ 2 ml/kg twice per week as CCl₄ administration groups and olive oil 2 ml/kg as controls. After 4 weeks, the livers of mice were removed under deep anesthesia and prepared for further studies such as histology, immunostaining, hydroxyproline assay, zymography and western blot analysis.
Results:  Mice lacking tPA developed more severe morphological injury and displayed an increased deposition of collagen in the liver after CCl₄ administration compared with wild-type counterparts. Deficiency of tPA increased α-smooth muscle actin expression in the mice livers. On the other hand, the decrease of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) activities, metalloproteinase-13 (MMP-13) expression and a marked increase of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) expression were found in the liver of CCl₄ administrated tPA^−/− mice compared with wild-type counterparts.
Conclusions:  Deficiency of tPA aggravated liver fibrosis through promoting hepatic stellate cells (HSCs) activation and inhibiting ECM degradation by decreasing MMP-2, MMP-9 activities and disrupting the balance between MMP-13 and TIMP-1.     

Addition of rosiglitazone to metformin is most effective in obese,insulin-resistant patients with type 2 diabetes

Aim:   These analyses were undertaken to evaluate the efficacy of the insulin sensitizer rosiglitazone (RSG) when added to the therapy of obese type 2 diabetes mellitus patients (T2D M ) taking near-maximal doses (2.5 g/day) of metformin (MET). In obese, insulin-resistant patients with T2D M who are inadequately controlled on MET, the addition of an agent that reduces insulin resistance may be a more rational and innovative approach than the addition of an insulin secretagogue.
Methods:   Data were pooled from two double-blind studies of RSG added to 2.5 g/day MET, involving a total of 550 T2D M patients. Patients were categorized as non-overweight, overweight and obese according to their baseline BMI using WHO criteria (<25 kgm⁻², 25–30 kgm⁻², >30 kgm⁻² respectively).
Results:   RSG improved glycaemia (HbA1c) and fasting plasma glucose (FPG) to a clinically significant extent in all three subgroups but the effect was most pronounced in the obese patients. Improvements in HOMA estimates of insulin resistance and beta-cell function were also greatest in the obese patients (4 mg: −16% and +19%; 8 mg: −37% and + 33% respectively), as were reductions in fasting insulin. The profile of adverse events was not demonstrably different in obese patients from the non-obese.
Conclusions:   In obese type 2 diabetic patients inadequately controlled on MET alone, addition of rosiglitazone improves glycaemic control, insulin sensitivity and beta-cell function to a clinically important extent.     

Magnitude of CD8+ T-cell responses against hepatitis C virus and severity of hepatitis do not necessarily determine outcomes in acute hepatitis C virus infection

Aim:  We investigated the relationship between the magnitude of comprehensive hepatitis C virus (HCV)-specific CD8⁺ T-cell responses and the clinical course of acute HCV infection.
Methods:  Six consecutive patients with acute HCV infection were studied. Analysis of HCV-specific CD8⁺ T-cell responses was performed using an interferon-γ-based enzyme-linked immunospot assay using peripheral CD8⁺ T-cells, monocytes and 297 20-mer synthetic peptides overlapping by 10 residues and spanning the entire HCV sequence of genotype 1b.
Results:  Five patients presented detectable HCV-specific CD8⁺ T-cell responses against a single and different peptide, whereas 1 patient showed responses against three different peptides. Neither the magnitude of HCV-specific CD8⁺ T-cell responses nor the severity of hepatitis predicts the outcome of acute hepatitis. The maximum number of HCV-specific CD8⁺ T-cells correlated with maximum serum alanine aminotransferase level during the course ( r  = 0.841, P  = 0.036).
Conclusions:  HCV-specific CD8⁺ T-cell responses were detectable in all 6 patients with acute HCV infection, and 6 novel HCV-specific CTL epitopes were identified. Acute HCV infection can resolve with detectable HCV-specific CD8⁺ T-cell responses, but without development of antibody against HCV.     

Carbocisteine can scavenge reactive oxygen species in vitro

Background and objective:   Reactive oxygen species (ROS) play an important role in the pathogenesis of various respiratory diseases. Carbocisteine, a mucoregulatory drug, is used in the treatment of several disease states but little information is available about its scavenger effects on ROS. The present study was designed to examine the scavenger effects of carbocisteine on ROS.
Methods:   The oxidation-reduction potential of carbocisteine was measured, and its scavenger effects on hypochlorous acid (HOCl), hydrogen peroxide (H₂O₂), hydroxyl radical (OH^•) and peroxynitrite (ONOO^-) were examined in cell-free conditions. The effects of carbocisteine on ROS generated from rat neutrophils, intracellular oxidative stress and release of inflammatory cytokines (IL-8 and IL-6) from IL-1β-induced airway epithelial cells, NCI-H292 cells, were investigated.
Results:   Carbocisteine provided a reducing stage and showed scavenger effects on H₂O₂, HOCl, OH^• and ONOO^- in cell-free conditions. Carbocisteine inhibited ROS generation from rat neutrophils, intracellular oxidative stress and release of IL-8 and IL-6 from NCI-H292 cells. N -acetyl- l -cysteine, a radical scavenger, also inhibited these events related to ROS as well as carbocisteine.
Conclusions:   These results suggest that carbocisteine could exert anti-inflammatory and anti-oxidant effects through directly scavenging ROS in addition to its previously known mucoregulatory effect.     

Adefovir plus lamivudine are more effective than adefovir alone in lamivudine-resistant HBeAg- chronic hepatitis B patients: A 4-year study

Background and Aim:  Adefovir dipivoxil (ADV) is effective in lamivudine (LAM)-resistant hepatitis B e antigen-negative (HBeAg^-) chronic hepatitis B (CHB). However, it is unclear whether LAM treatment should be continued in these patients. We aimed to compare the long-term efficacy of adding ADV to ongoing LAM treatment versus switching to ADV monotherapy in LAM-resistant HBeAg^- CHB.
Methods:  Sixty LAM-resistant patients with HBeAg^- CHB were randomly assigned (3:1) to combination therapy (10 mg ADV once daily plus ongoing LAM at 100 mg once daily [ n  = 45]) or 10 mg ADV monotherapy once daily ( n  = 15). Virological and biochemical responses were defined as hepatitis B virus (HBV)–DNA <400 copies/mL and as normalization of alanine aminotransferase levels, respectively.
Results:  The median follow-up time was 53 months (range 20–60 months). A virological response was observed in 38/45 (84.4%) and 11/15 (73.3%) patients in the ADV/LAM and ADV monotherapy groups, respectively ( P  = 0.56). Biochemical response rates were higher in the ADV/LAM group than in the ADV monotherapy group (90.9% vs 57.1%, respectively; P  = 0.01). In the ADV/LAM group, serum HBV–DNA remained undetectable in all patients who achieved a virological response ( n  = 38). In the ADV monotherapy group, virological breakthrough occurred in four of the 11 patients who achieved a virological response (36.4%; P  < 0.001 vs the ADV/LAM group, log–rank test). In addition, two patients in each group who did not achieve a virological response eventually developed ADV resistance.
Conclusions:  Adding ADV to LAM is more effective than switching to ADV monotherapy in LAM-resistant patients with HBeAg^- CHB.     

Is acute appendicitis another inflammatory condition associated with highly active antiretroviral therapy (HAART)?

  ¹ Department of Genitourinary Medicine, St George's Hospital, London, UK,   ² Department of Infectious Diseases, Cork University Hospital, Cork, Ireland,   ³ Department of Infectious Diseases and   ⁴ Department of Histopathology, St George's Hospital, London, UK
Objective   To report the occurrence of acute appendicitis as a possible manifestation of the immune restoration inflammatory syndrome (IRIS) following the commencement of highly active antiretroviral therapy (HAART) in HIV patients.
Design   Case-note review of HIV patients on HAART with acute appendicitis.
Methods   Review of HIV markers, antiretroviral therapy and abdominal ultrasound results of four HIV patients with acute appendicitis and the histopathology reports on the appendix in two of the patients.
Results   From a population of approximately 350 HIV patients on HAART, we found four patients who developed acute appendicitis within 6 months of commencing or changing HAART.
Conclusion   Acute appendicitis occurring in HIV patients on HAART may represent a variant of IRIS. Further immunohistopathological and epidemiological evaluation will be needed to define this relationship fully.