Chimbayo, Elizabeth T

Chirambo, Aaron P

Jambo, Kondwani

Kajanga, Cheusisime

Mallewa, Jane

Mandalasi, Christine

Masamba, Leo

Mhango, David V

Mitini-Nkhoma, Steven C

Mwandumba, Henry

Mzinza, David T

Russell, David G

Squire, Bertie

Tembo, Dumizulu L

PubMed

LSTM Online Archive

CorrespondenceAIDS 2022, 36:2229–2233Latent tuberculosis infection among adults attending HIV services at an urban tertiary hospital in MalawiActive tuberculosis (TB) can develop from newlyacquired Mycobacterium tuberculosis infection or fromreactivation of pre-existing latent TB infection (LTBI).Although individuals with LTBI do not have clinical TBsymptoms, they are a reservoir for active TB cases andpose a significant challenge to the global effort toeliminate TB. Strategies to reduce the burden of TB varyamong countries, and are, in part, determined by the localprevalence of LTBI and active TB [1]. Developing suchstrategies for sub-Saharan African (SSA) countries ischallenging because of the paucity of data on theprevalence of LTBI in the region [2]. To address thisknowledge gap, we conducted a cross-sectional study todetermine the prevalence of, and factors associated withLTBI among asymptomatic people with HIV (PWH) andhealthy, HIV-uninfected adults attending antiretroviraltherapy (ART) and HIV voluntary counselling andtesting clinics at Queen Elizabeth Central Hospital, alarge urban tertiary hospital in Blantyre, Malawi.All study participants were Malawian adults aged at least18 years who had received Bacillus Calmette-Guerinvaccination during childhood but had no history ofprevious TB treatment or clinical and laboratory evidenceof active TB. They were tested for LTBI using theQuantiFERON-TB Gold Plus (QFT-Plus) interferongamma release assay (IGRA) (QIAGEN, Hilden,Germany) according to the manufacturer’s instructions.Informed written consent was obtained from allparticipants and the study protocol was approved bythe College of Medicine Research Ethics Committee inMalawi (protocol P.02/18/2356) and the LiverpoolSchool of Tropical Medicine Research Ethics Committeein the UK (protocol 17-032).We recruited 165 participants, 66 (40%) of whom werePWH. Of the 66 PWH, 55 (83.3%) were on ART. Tenparticipants, six of whom were PWH, had indeterminateQFT-Plus results and were excluded from further analysis.Of the remaining 155 individuals, 68 [43.87% [95%confidence interval (CI) 35.92–52.06] had positive QFT-Plus results, indicating that they had LTBI. Subgroupanalysis by sex revealed that LTBI was more prevalentamong males than females [46 of 88 males (52.27%, 95%CI 41.35–63.04) vs. 22 of 67 females (32.84%, 95% CI21.85–45.40), P¼ 0.02]. However, the prevalence ofLTBI was similar across different age groups (P¼ 0.82,Fig. 1a) and between PWH and HIV-uninfectedindividuals [48.33% (95% CI 35.23–61.61) vs. 41.05%(95% CI 31.06–51.62), P¼ 0.37].Next, we performed multiple logistic regression todetermine if LTBI was associated with age, sex, HIVstatus, plasma HIV viral load or peripheral blood CD4þT-cell count. We found that HIV infection, male sex andundetectable HIV viral load were independent risk factorsfor LTBI [odds ratio (OR) 6.81, CI 1.79–28.66,P¼ 0.006; OR 3.02, CI 1.41–6.77, P¼ 0.006; OR4.49, CI 1.23–19.36, P¼ 0.03, respectively, Fig. 1b],while age and CD4þ T-cell count were not.The current study reports a high prevalence of LTBIamong adults attending HIV services at an urbanhospital in Malawi, a country with high TB and HIVprevalence. Our findings are consistent with previousreports from Nigeria [3] and Zimbabwe [4]. AlthoughHIV infection is a known risk factor for active TB [5],we show that it is also a risk factor for LTBI. The highburden of LTBI among PWH in SSA justifies the WHOrecommendation of preventive treatment for LTBI inPWH even in the absence of IGRA or tuberculin skintest results [6].The high prevalence of LTBI in SSA is likely indicative ofhigh community transmission of TB. Currently, mostcountries in the region treat PWH with isoniazidpreventive therapy (IPT) for 6–36 months [7–9].Although IPT significantly reduces the risk of LTBIprogressing to active TB, its protective effect wanesfollowing discontinuation [10]. Therefore, lifelong IPTwould provide PWHwith long-lasting protection againstactive TB. In addition, the high LTBI prevalence amongHIV-uninfected adults calls for a review of the publichealth response to TB in the region. Treatment of LTBI inother at-risk groups should be explored to reduce thereservoir for active TB cases.We acknowledge that the small sample size and thehospital-based recruitment may limit generalizability ofour study findings, therefore large community-basedstudies are required to determine the communityprevalence of LTBI in Malawi. Nonetheless, ourparticipants were ambulatory and reflect the compositionof the communities served by the hospital.In conclusion, the prevalence of LTBI in the studypopulation was high. Males and PWHwere at high risk ofLTBI. Treating individuals with LTBI in SSA, includinglifelong IPT for PWH should complement current activeTB case finding strategies to reduce TB incidence anddeaths in the region.ISSN 0269-9370 Copyright Q 2022 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under theCreative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the originalwork is properly cited. 2229AcknowledgementsH.C.M. conceived and designed the experiments. S.C.M.-N., D.T.M., E.T.C. and A.P.C. performed theexperiments and analysed the data. S.C.M.-.N. and H.C.M. wrote the article, with input from D.T.M., E.T.C.,A.P.C., D.V.M., C.K., C.M., D.L.T., J.M., L.M., D.G.R.,K.C.J. and S.B.S. The authors thank all study participantsand staff of the Clinical Investigation Unit, MalawiLiverpool Wellcome Clinical Programme, KamuzuUniversity of Health Sciences and Queen ElizabethCentral Hospital for their support and co-operationduring the study.The current work was supported by an African ResearchLeader Award MR/P020526/1 awarded to H.C.M. andS.B.S., jointly funded by the UK Medical ResearchCouncil (MRC) and the UK Department for Interna-tional Development (DFID) under the MRC/DFIDConcordant agreement and are part of the EDCTP2programme supported by the European Union. Thework was also supported by the National Institutes ofHealth (USA) award AI155319 to D.G.R. A core grant206545/Z/17/Z from Wellcome supports the MalawiLiverpool Wellcome Clinical Research Programme.Conflicts of interestThere are no conflicts of interest.Steven C. Mitini-Nkhomaa,M, David T. Mzinzaa,M,Elizabeth T. Chimbayoa, Aaron P. Chiramboa, DavidV. Mhangoa, Cheusisime Kajangaa, Christine Manda-lasia, Dumizulu L. Temboa, Jane Mallewab, LeoMasambab, David G. Russellc, Kondwani C. Jamboa,d,S. Bertie Squired and Henry C. Mwandumbaa,b,d,aMalawi Liverpool Wellcome Clinical Research Pro-gramme, Kamuzu University of Health Sciences,bDepartment of Medicine, Kamuzu University ofHealth Sciences and Queen Elizabeth Central Hospital,Blantyre, Malawi, cMicrobiology and Immunology,College of Veterinary Medicine, Cornell University,Ithaca, NY, USA, and dDepartment of ClinicalSciences, Liverpool School of Tropical Medicine,Liverpool, UK.Received: 19 February 2022; revised: 19 April 2022;accepted: 18 May 2022.References1. World Health Organisation. Guidelines on the management oflatent tuberculosis infection. Geneva: World Health Organisa-tion; 2015.2. Basera TJ, Ncayiyana J, Engel ME. Prevalence and risk factors oflatent tuberculosis infection in Africa: a systematic review andmeta-analysis protocol. BMJ Open 2017; 7:e012636.3. Aladesanmi AO, Ojuawo OB, Aladesanmi OO, Fawibe AE,Desalu OO, Ojuawo AB, et al. Diagnosis of latent tuberculosisamong HIV-infected patients in Ilorin, Nigeria using tuberculinskin test and interferon gamma release assay. Pan Afr Med J2021; 38:264.4. Dodd PJ, Millington KA, Ghani AC, Mutsvangwa J, ButterworthAE, Lalvani A, et al. Interpreting tuberculin skin tests in apopulation with a high prevalence of HIV, tuberculosis, andnonspecific tuberculin sensitivity. Am J Epidemiol 2010;171:1037–1045.5. World Health Organisation. Global tuberculosis report 2021.Geneva: World Health Organisation; 2021.6. World Health Organisation. Latent tuberculosis infection: up-dated and consolidated guidelines for programmatic manage-ment. Geneva: World Health Organisation; 2019.2230 AIDS 2022, Vol 36 No 15(a) (b)<3131- 4041- 50>50020406080100LTBIPrevalence(%)Age (Years)AgeCD4+T cell countDuration of ARTHIVstatusMale genderUndetectableHIVviral load0.1110100Risk factorsOddsratioFig. 1. (a) Prevalence of latent tuberculosis infection according to age. (b) Multivariate logistic regression analysis of risk factorsof latent tuberculosis infection. Error bars: 95% confidence interval. NU60 HIV-positive; 95 HIV-negative.Correspondence to Henry C. Mwandumba, Malawi LiverpoolWellcome Clinical Research Programme, Kamuzu Universityof Health Sciences, PO Box 30096, Chichiri, Blantyre 3,Malawi. Tel: +265 1 876 444/þ265 881 073 822;e-mail: Henry.Mwandumba@lstmed.ac.uk S.C.M-N. and D.T.M. contributed equally to the article.7. Sabasaba A, Mwambi H, Somi G, Ramadhani A, Mahande MJ.Effect of isoniazid preventive therapy on tuberculosis inci-dence and associated risk factors among HIV infected adultsin Tanzania: a retrospective cohort study. BMC Infect Dis 2019;19:62.8. Hsieh YL, Jahn A, Menzies NA, Yaesoubi R, Salomon JA, GirmaB, et al. Evaluation of 6-month versus continuous isoniazidpreventive therapy for Mycobacterium tuberculosis in adultsliving with HIV/AIDS in Malawi. J Acquir Immune Defic Syndr2020; 85:643–650.9. Yanes-Lane M, Ortiz-Brizuela E, Campbell JR, Benedetti A,Churchyard G, Oxlade O, et al. Tuberculosis preventive therapyfor people living with HIV: a systematic review and networkmeta-analysis. PLoS Med 2021; 18:e1003738.10. Samandari T, Agizew TB, Nyirenda S, Tedla Z, Sibanda T,Mosimaneotsile B, et al. Tuberculosis incidence after 36months’isoniazid prophylaxis in HIV-infected adults in Botswana: aposttrial observational analysis. AIDS 2015; 29:351–359.DOI:10.1097/QAD.0000000000003359Correspondence 2231CorrespondenceAIDS 2022, 36:2229–2233Doravirine/lamivudine/tenofovir disoproxil fumarate-induced hypertriglyceridemia in a newly diagnosedAIDS patientA 44-year-old woman (male-to-female) affected byhypertension and asthma with history of unprotectedsexual intercourse and inhalatory drug abuse was admittedto the emergency room complaining of nausea, headache,and convulsive status epilepticus. Brain computedtomography (CT) scan showed hypodense lesions inthe left parietal lobe and left cerebellar hemisphere,compatible with a central nervous system opportunisticinfection. Fourth-generation HIV test was positive andfurther confirmed by immunoblotting (baseline absolutelymphocyte count 1256 cell/ml; CD3þCD4þ count 52cells/ml; CD4þ/CD8þ ratio 0.06 with HIV-1-RNA:407 000 copies/ml). Intravenous valproic acid, levetira-cetam and lacosamide were started as antiepileptictherapy. Furthermore, intravenous mannitol was admin-istered for the reduction of intracranial pressure resultingfrom cerebral edema. PCR for Toxoplasma spp. testedpositive on whole blood sample, and even thoughcerebrospinal fluid analysis was unfeasible because ofcompressive phenomena on the left brain fourth ventricle,a diagnosis of neurotoxoplasmosis was made. Severalactive infections were also diagnosed, including severeacute respiratory syndrome coronavirus 2 (SARS-CoV-2), hepatitis B virus (HBV) (because of the presence ofHBs, HBe antigens, HBe antibodies and HBV-DNA72UI/ml), cytomegalovirus (with detectable viremia) andpulmonary aspergillosis. Active and latent infectionbecause of Mycobacterium tuberculosis was ruled out.Considering the need for prophylactic treatments andthe presence of multiple active infections, the patientreceived secondary prophylaxis for SARS-CoV2 with asingle dose of sotrovimab (VIR-7831). Treatment forpulmonary aspergillosis was started with isavuconazole,and trimethoprim–sulfamethoxazole was introduced forthe treatment of neurotoxoplasmosis. Prophylaxis forMycobacterium avium complex was also provided with oralazithromycin. Antiretroviral treatment (ART) withdoravirine/lamivudine/tenofovir disoproxil fumarate(DOR/3TC/TDF) association as fixed-dose combina-tion single-tablet regimen (Delstrigo-Merck Canada Inc.)was initiated. Nevertheless, during the following routineblood test, an unexpected increase in triglyceride valuewas noted, which spiked up to 1719mg/dl on the 15thday after the introduction of DOR/3TC/TDF. No signor symptom of acute pancreatitis was detected at any timeduring hospitalization. A differential diagnosis was madebetween a previously undiagnosed familial hypertrigly-ceridemia and drug-related toxicity. A complete lipidprofile was performed at admission revealing an isolatedmild hypertriglyceridemia (admission triglyceride value276mg/dl, reference range <150mg/dl); therefore, thefirst diagnostic hypothesis was excluded. In an attempt toidentify the drug putatively responsible for the suddenincrease in triglyceride levels, therapy was simplified withsequential sampling of blood triglycerides. No improve-ment was observed after isavuconazole, azithromycin orvalproic acid suspension. Considering the whole thera-peutic scheme, after a literature search for possibleinteractions and side effects, we safely assumed hyper-triglyceridemia as unrelated side effect of any of theremaining drugs, including levetiracetam, lacosamide andtrimethoprim–sulfamethoxazole [1,2]. This led us toevaluate the possible involvement of DOR/3TC/TDF.Considering the increased risk of acute pancreatitisbecause of hypertriglyceridemia, plasma apheresis wassuggested. Nevertheless, the patient refused the treat-ment. The simultaneous interruption of DOR/3TC/TDF together with the introduction of gemfibrozilcaused a rapid decrease in triglyceride levels (Fig. 1).According to fenofibrate effect on lowering triglyceridelevels, reported, on a sample of 1113 patients with a 4months median follow-up, a median reduction oftriglycerides of 60% (P< 0.001) [3]. Conversely,our patient reported a reduction of 87.5% on triglyceridelevels in less than 2 weeks, further reinforcingour hypothesis of a drug-induced isolated hypertrigly-ceridemia.We therefore proceeded with a treatment re-challengewith DOT/3TC/TDF in combination with gemfibrozil,with a new rapid increase in triglyceride levels, implying adirect effect of DOR/3TC/TDF on triglyceride levels:This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or usedcommercially without permission from the journal.

Latent tuberculosis infection among adults attending HIV services at an urban tertiary hospital in Malawi.

Mitini-Nkhoma, Steven C.

Mzinza, David T.

Chimbayo, Elizabeth T.

Chirambo, Aaron P.

Mhango, David V.

Tembo, Dumizulu L.

Russell, David G.

Jambo, Kondwani C.

Squire, S. Bertie

Mwandumba, Henry C.

PubMed Central

Latent tuberculosis infection among adults attending HIV services at an urban tertiary hospital in Malawi

https://archive.lstmed.ac.uk/21570/1/Latent_tuberculosis_infection_among_adults.20.pdf

Latent tuberculosis infection among adults attending HIV services at an urban tertiary hospital in Malawi.

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