Malaria & HIV among Pediatric Inpatients in Two Tanzanian Referral Hospitals

Malaria remains common in sub-Saharan Africa, but it is frequently over-diagnosed and over-treated in hospitalized children. HIV is prevalent in many malaria endemic areas and may delay parasite clearance and increase mortality among children with malaria. 

This prospective cohort study enrolled children with suspected malaria between 3 months and 12 years of age hospitalized at two referral hospitals in Tanzania. Both a thick blood smear (BS) and a malaria rapid diagnostic test (mRDT) were performed. If discordant results were obtained, PCR was performed for Plasmodium falciparum. Malaria was confirmed if two out of three tests were positive. Malaria parasite densities were determined for two consecutive days after diagnosis and treatment of malaria. All participants were tested for HIV. 

Among 1492 hospitalized children, 400 (26.8%) were enrolled with suspected malaria infection. There were 196/400 (49.0%) males, and the median age was 18 [9-36] months. BS was positive in 95/400 (23.8%), and mRDT was positive in 70/400 (17.5%), with moderate agreement (Kappa=0.598). Concordant results excluded malaria in 291/400 (72.8%) and confirmed malaria in 56/400 (14.0%). PCR performed on 53 discordant results confirmed malaria in 1/39 of the BS-positive/mRDT-negative cases, and 6/14 of the BS-negative/mRDT-positive cases. 

The prevalence of confirmed malaria was 63/400 (15.8%). In multivariable logistic regression, malaria was associated with HIV (OR 3.45 [1.65-7.20], p=0.001). Current breastfeeding (OR 0.25 [0.11-0.56], p=0.001) and higher hemoglobin (OR 0.70 [0.60-0.81], p<0.001 per 1g/dL) were associated with decreased odds of malaria. Malaria parasite clearance was delayed in HIV-infected participants (p<0.001). Malaria is over-diagnosed even at referral centers in high transmission areas. 

Hospitalized HIV-infected children are more likely to have malaria and exhibit delayed clearance of parasites. Hospitals should consider using mRDTs as a first step for malaria testing among hospitalized children in sub-Saharan Africa.

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By:  Smart LR1, Orgenes N2, Mazigo HD3, Minde M4, Hokororo A5, Shakir M6, Verweij JJ7, Downs JA8, Peck RN8.

• 1Department of Internal Medicine, Catholic University of Health & Allied Sciences, P.O. Box 1464, Mwanza, Tanzania; Department of Internal Medicine, Bugando Medical Centre, P.O. Box 1370, Mwanza, Tanzania; Center for Global Health, Weill Cornell Medical College, 402 East 67th Street, 2nd Floor, NewYork, NY 10065, USA. Electronic address: smart.luke@gmail.com.
• 2Department of Pediatrics, Catholic University of Health & Allied Sciences, P.O. box 1464, Mwanza, Tanzania.
• 3Department of Parasitology, Catholic University of Health & Allied Sciences, P.O. Box 1464, Mwanza, Tanzania.
• 4Department of Pediatrics, Bugando Medical Centre, P.O. Box 1370, Mwanza, Tanzania.
• 5Department of Pediatrics, Catholic University of Health & Allied Sciences, P.O. box 1464, Mwanza, Tanzania; Department of Pediatrics, Bugando Medical Centre, P.O. Box 1370, Mwanza, Tanzania.
• 6Weill Cornell Medical College in Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha, Qatar.
• 7Laboratory of Medical Microbiology and Immunology, St. Elisabeth Hospital, Tilburg, The Netherlands.
• 8Department of Internal Medicine, Catholic University of Health & Allied Sciences, P.O. Box 1464, Mwanza, Tanzania; Department of Internal Medicine, Bugando Medical Centre, P.O. Box 1370, Mwanza, Tanzania; Center for Global Health, Weill Cornell Medical College, 402 East 67th Street, 2nd Floor, NewYork, NY 10065, USA. 
• Acta Trop. 2016 Mar 18;159:36-43. doi: 10.1016/j.actatropica.2016.03.019.

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Missed Opportunities of Inclusion of HIV-Infected Children to Initiate Antiretroviral Treatment Before the Age of Two in West Africa, 2011 to 2013

INTRODUCTION:

The World Health Organization (WHO) 2010 guidelines recommended to treat all HIV-infected children less than two years of age. We described the inclusion process and its correlates of HIV-infected children initiated on early antiretroviral therapy (EART) at less than two years of age in Abidjan, Côte d'Ivoire, and Ouagadougou, Burkina Faso.

METHODS:

All children with HIV-1 infection confirmed with a DNA PCR test of a blood sample, aged less than two years, living at a distance less than two hours from the centres and whose parents (or mother if she was the only legal guardian or the legal caregiver if parents were not alive) agreed to participate in the MONOD ANRS 12206 project were included in a cohort to receive EART based on lopinavir/r. We used logistic regression to identify correlates of inclusion.

RESULTS:

Among the 217 children screened and referred to the MONOD centres, 161 (74%) were included and initiated on EART. The main reasons of non-inclusion were fear of father's refusal (48%), mortality (24%), false-positive HIV infection test (16%) and other ineligibility reasons (12%). Having previously disclosed the child's and mother's HIV status to the father (adjusted odds ratio (aOR): 3.20; 95% confidence interval (95% CI): 1.55 to 6.69) and being older than 12 months (aOR: 2.05; 95% CI: 1.02 to 4.12) were correlates of EART initiation. At EART initiation, the median age was 13.5 months, 70% had reached WHO Stage 3/4 and 57% had a severe immune deficiency.

CONCLUSIONS:

Fear of stigmatization by the father and early competing mortality were the major reasons for missed opportunities of EART initiation. There is an urgent need to involve fathers in the care of their HIV-exposed children and to promote early infant diagnosis to improve their future access to EART and survival.

Below:  Cohort profile ofthe ANRS 12206 MONOD study, Abidjan, Ouagadougou, May 2011 to February 2013

Full article at:   http://goo.gl/ILmMTv

By:  Dahourou DL1,2,3, Amorissani-Folquet M4,5, Coulibaly M1,2, Avit-Edi D4, Meda N1,6,7, Timite-Konan M8, Arendt V9, Ye D7,10, Amani-Bosse C4, Salamon R2,Lepage P11, Leroy V12; Monod Anrs 12206 Study Group.

• 1MONOD Project, ANRS 12206, Centre de Recherche Internationale pour la Santé, Ouagadougou, Burkina Faso.
• 2Inserm, U1219, Institut de Santé Publique, Epidémiologie et Développement, University of Bordeaux, Bordeaux, France.
• 3Centre Muraz, Bobo-Dioulasso, Burkina Faso; ddahourou@gmail.com; ddahourou@gmail.com.
• 4PACCI Programme, Site ANRS, Projet Monod, Abidjan, Côte d'Ivoire.
• 5Pediatric Department, CHU of Cocody, Abidjan, Côte d'Ivoire.
• 6Centre Muraz, Bobo-Dioulasso, Burkina Faso.
• 7University of Ouagadougou, Ouagadougou, Burkina Faso.
• 8Pediatric Department, Centre Hospitalier Universitaire (CHU) de Yopougon, Abidjan, Côte d'Ivoire.
• 9Department of Infection and Immunity, Luxembourg Institute of Health, Luxembourg.
• 10Pediatric Department, CHU Charles de Gaulle, Ouagadougou, Burkina Faso.
• 11Pediatric Department, Hôpital Universitaire des Enfants de la Reine Fabiola, Université Libre de Bruxelles, Brussels, Belgium.
• 12Inserm, U1027, Université Toulouse, Toulouse, France. 
• J Int AIDS Soc. 2016 Mar 23;19(1):20601. doi: 10.7448/IAS.19.1.20601.

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Tuberculosis Incidence Is High in HIV-Infected African Children But Is Reduced by Co-Trimoxazole & Time on Antiretroviral Therapy

BACKGROUND:

There are few data on tuberculosis (TB) incidence in HIV-infected children on antiretroviral therapy (ART). Observational studies suggest co-trimoxazole prophylaxis may prevent TB, but there are no randomized data supporting this. The ARROW trial, which enrolled HIV-infected children initiating ART in Uganda and Zimbabwe and included randomized cessation of co-trimoxazole prophylaxis, provided an opportunity to estimate the incidence of TB over time, to explore potential risk factors for TB, and to evaluate the effect of stopping co-trimoxazole prophylaxis.

METHODS:

Of 1,206 children enrolled in ARROW, there were 969 children with no previous TB history. After 96 weeks on ART, children older than 3 years were randomized to stop or continue co-trimoxazole prophylaxis; 622 were eligible and included in the co-trimoxazole analysis. Endpoints, including TB, were adjudicated blind to randomization by an independent endpoint review committee (ERC). Crude incidence rates of TB were estimated and potential risk factors, including age, sex, center, CD4, weight, height, and initial ART strategy, were explored in multivariable Cox proportional hazards models.

RESULTS:

After a median of 4 years follow-up (3,632 child-years), 69 children had an ERC-confirmed TB diagnosis. The overall TB incidence was 1.9/100 child-years (95 % CI, 1.5-2.4), and was highest in the first 12 weeks following ART initiation (8.8/100 child-years (5.2-13.4) versus 1.2/100 child-years (0.8-1.6) after 52 weeks). A higher TB risk was independently associated with younger age (<3 years), female sex, lower pre-ART weight-for-age Z-score, and current CD4 percent; fewer TB diagnoses were observed in children on maintenance triple nucleoside reverse transcriptase inhibitor (NRTI) ART compared to standard non-NRTI + 2NRTI. Over the median 2 years of follow-up, there were 20 ERC-adjudicated TB cases among 622 children in the co-trimoxazole analysis: 5 in the continue arm and 15 in the stop arm (hazard ratio (stop: continue) = 3.0 (95 % CI, 1.1-8.3), P = 0.028). TB risk was also independently associated with lower current CD4 percent (P <0.001).

CONCLUSIONS:

TB incidence varies over time following ART initiation, and is particularly high during the first 3 months post-ART, reinforcing the importance of TB screening prior to starting ART and use of isoniazid preventive therapy once active TB is excluded. HIV-infected children continuing co-trimoxazole prophylaxis after 96 weeks of ART were diagnosed with TB less frequently, highlighting a potentially important role of co-trimoxazole in preventing TB.

Below:  Tuberculosis incidence over time after antiretroviral therapy initiation

Full article at:   http://goo.gl/vd6abn

By:  Crook AM1, Turkova A2, Musiime V3,4, Bwakura-Dangarembizi M5, Bakeera-Kitaka S4,6, Nahirya-Ntege P7, Thomason M2, Mugyenyi P3, Musoke P4,8,Kekitiinwa A6, Munderi P7, Nathoo K5, Prendergast AJ9, Walker AS2, Gibb DM2; ARROW Trial Team.

• 1MRC Clinical Trials Unit at UCL, London, UK. angela.crook@ucl.ac.uk.
• 2MRC Clinical Trials Unit at UCL, London, UK.
• 3Joint Clinical Research Centre, Kampala, Uganda.
• 4Makerere University College of Health Sciences, Kampala, Uganda.
• 5Department of Paediatrics and Child Health, University of Zimbabwe Medical School, Harare, Zimbabwe.
• 6Baylor College of Medicine Children's Foundation, Kampala, Uganda.
• 7MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
• 8MU-JHU Care Ltd, Kampala, Uganda.
• 9Blizard Institute, Queen Mary University of London, London, UK. 
• BMC Med. 2016 Mar 23;14(1):50. doi: 10.1186/s12916-016-0593-7.

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Children & Young People with Perinatal HIV In Europe: Epidemiological Situation in 2014 & Implications for the Future

Accurate ascertainment of the number of children living with human immunodeficiency virus (HIV) is important to plan paediatric and adolescent health services. In Europe, the first generation of perinatally HIV-infected survivors are transferring to adult care and their health needs are unknown. 

We undertook an online survey of HIV cohort studies participating in the EuroCoord Network of Excellence to ascertain the number of perinatally HIV-infected (pHIV) patients included, to compare it with those published by the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) and to assess the ability of countries to follow up pHIV patients after transfer to adult care. At the end of 2013, 16 countries in EuroCoord reported 8,229 pHIV patients in follow-up in cohorts, compared with 5,160 cumulative diagnoses reported by the ECDC in the same area. Follow-up of pHIV patients after transfer to adult care varied. It is likely that the number of diagnoses of perinatal HIV reported to ECDC is an underestimate, although this varies by country. 

Further work is needed to refine estimates and encourage follow-up in adult HIV cohorts to investigate long-term outcomes and improve the care of the next generation of children with HIV.

Below:  Number of perinatal patients in HIV cohorts in countries in the EU/EEA area, to end of 2013 (n = 8,229)

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By:  Ali Judd (PENTA-EPPICC), Intira Jeannie Collins (PENTA-EPPICC), Sara Lodi (CASCADE), Ashley Olson (CASCADE), Nikos Pantazis (CASCADE), Julia del Amo (COHERE), Charlotte Duff (PENTA-EPPICC), Anne-Francoise Gennotte (EuroSIDA), Dennis Kristensen (EuroSIDA), Bruno Ledergerber (EuroSIDA), David Nadal (EuroSIDA), Pablo Rojo Conejo (COHERE), Caroline Sabin (COHERE), Yacine Saidi (PENTA-EPPICC), Rikke Salbøl Brandt (COHERE), Monique Termote (COHERE), Claire Thorne (PENTA-EPPICC), Josiane Warszawski (COHERE), Diana M Gibb (PENTA-EPPICC).

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Prevention & Care of Pediatric HIV Infection in Ouagadougou, Burkina Faso: Knowledge, Attitudes & Practices of the Caregivers

Background

The paediatric Human Immunodeficiency Virus (HIV) epidemic still progresses because of operational challenges in implementing prevention of mother-to-child HIV transmission (PMCT) programs. We assessed the knowledge, attitudes and practices (KAP) of children’s caregivers regarding mother-to-child transmission (MTCT) of HIV, paediatric HIV infection, early infant diagnosis (EID), and paediatric antiretroviral treatment in Ouagadougou, Burkina Faso.

Methods

We undertook a qualitative survey in the four public hospitals managing HIV exposed or infected children, in Ouagadougou in 2011. A sociologist used a semi-structured questionnaire to interview caregivers of children less than 5 years old attending the paediatrics wards on their KAP. Study participants were divided into four groups as follows:

those who did not yet know their children’s HIV infection status, those who were waiting for their children’s HIV test results, those who were waiting for antiretroviral treatment, and those who were already on antiretroviral treatment.

Results

A total of 37 caregivers were interviewed. The mean age was 32.5 years, and 29 (78 %) were mothers. Twenty seven (73 %) caregivers had primary or higher level of education, and 15 (40 %) described their occupation as “housewife”. Overall, 36 (97 %) of caregivers knew that the main route of HIV transmission for infants was through MTCT and 14 (38 %) specified that it occurred during pregnancy or delivery. Five percent thought that MTCT of HIV occurred during conception. PMTCT interventions could help prevent infant HIV infection according to 32 (87 %) caregivers. Thirty five percent of caregivers stated EID as a prevention strategy. Fifty-four percent of the participants believed that replacement feeding option would prevent MTCT of HIV; 24 (65 %) stated that they would prefer medical practitioners seek caregivers’ consent before carrying out any HIV-test for their child, and that caregivers’ consent was not compulsory before antiretroviral treatment. All caregivers thought that it was necessary to treat HIV-infected children, although they did not know what interventions could be done.

Conclusions

This study highlighted the low level of caregivers’ knowledge on paediatric HIV prevention and care in Ouagadougou. Awareness programs targeting caregivers need to be strengthened in order to improve the uptake of HIV early infant diagnosis and care.

Caregivers’ knowledge, attitudes and perceptions in Ouagadougou, Burkina Faso, 2011

	Total N = 37 100 %	Group 1 N = 11 100 %	Group 2 N = 4 100 %	Group 3 N = 5 100 %	Group 4 N = 17 100 %	Groups 1 + 2 + 3 N = 20 100 %	P-value (Group 1 + 2 + 3 vs Group 4)
Caregiver’s knowledge of existing interventions to prevent MTCT of HIV
Yes	30 (81)	7 (64)	4 (100)	3 (60)	16 (94)	14 (70)	0.16
No	1 (3)	0 (0)	0 (0)	1 (20)	0 (0)	1 (5)
No response	6 (16)	4 (36)	0 (0)	1 (20)	1 (6)	5 (25)
Caregiver’s knowledge regarding existing methods of infant HIV diagnosis
Yes	32 (86)	8 (73)	4 (100)	5 (100)	15 (88)	17 (85)	0.77
No	5 (14)	3 (27)	0 (0)	0 (0)	2 (12)	3 (15)
Caregiver’s knowledge regarding existing treatment of HIV-infected infants
Yes	37 (100)	11 (100)	4 (100)	5 (100)	17 (100)		Not applicable
No	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
Caregiver’s attitude regarding the practice of their child systematic HIV testing
For	31 (84)	11 (100)	3 (75)	4 (80)	13 (76)	18 (90)	0.26
Against	6 (16)	0 (0)	1 (25)	1 (20)	4 (24)	2 (10)
Caregiver’s attitude regarding the antiretroviral treatment of HIV-infected children
For	37 (100)	11 (100)	4 (100)	5 (100)	17 (100)	20 (100)	Not applicable
Against	0 (0)	0 (0)	0 (0)	0 (0.0)	0 (0.0)	0 (0)
Parent’s consent needed for child HIV-test
Yes	24 (65)	8 (73)	3 (75)	4 (80)	9 (53)	15 (75)	0.16
No	13 (35)	3 (27)	1 (25)	1 (20)	8 (47)	5 (25)
Parent’s consent needed for child treatment
Yes	11 (30)	6 (55)	0 (0)	1 (20)	4 (24)	7 (35)	0.25
No	24 (65)	4 (36)	3 (75)	4 (80)	13 (76)	11 (55)
No response	2 (5)	1 (9)	1 (25)	0 (0)	0 (0)	2 (10)

Group 1: caregivers of HIV-infected child currently treated with antiretroviral therapy

Group 2: caregivers of HIV-infected child not yet initiated on antiretroviral therapy

Group 3: caregivers waiting for their child’s HIV post-test result

Group 4: caregivers attending paediatric ward, with an unknown HIV child status

Vs versus

Full article at:   http://goo.gl/1Dwg43

By:  Malik Coulibaly, Elisabeth Thio, Caroline Yonaba, Sylvie Ouédraogo, Nicolas Meda, Fla Kouéta, Désiré Lucien Dahourou, Angèle Kalmogho, Mady Gansonré, Diarra Yé, Ludovic Kam, Valériane Leroy, and for the MONOD Study Group*

Projet MONOD, ANRS 12206, Centre de Recherche Internationale pour la Santé, 09 BP 168 Ouagadougou, Burkina Faso

Centre Muraz, Bobo Dioulasso, Burkina Faso

CHU Charles De Gaules, Service de Pédiatrie médicale, Ouagadougou, Burkina Faso

CHU Yalgado Ouédraogo, Service de Pédiatrie, Ouagadougou, Burkina Faso

Inserm U1219, Institut de Santé Publique, Epidémiologie et Développement, Université de Bordeaux, Bordeaux, France

Inserm U1027 Université Paul Sabatier, Toulouse 3, Toulouse, France

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Antiretroviral Stewardship in a Pediatric HIV Clinic: Development, Implementation, and Improved Clinical Outcomes

BACKGROUND:

Antiretroviral (ARV) management in pediatrics is a challenging process in which multiple barriers to optimal therapy can lead to poor clinical outcomes. In a pediatric HIV clinic, we implemented a systematic ARV stewardship program to evaluate ARV regimens and make recommendations for optimization when indicated.

METHODS:

A comprehensive assessment tool was used to screen for issues related to genotypic resistance, virologic/immunologic response, drug-drug interactions, side effects, and potential for regimen simplification. The ARV stewardship team (AST) made recommendations to the HIV clinic provider, and followed patients prospectively to assess clinical outcomes at 6 and 12 months.

RESULTS:

The most common interventions made by the AST included regimen optimization in patients on suboptimal regimens based on resistance mutations (35.4%), switching to safer ARVs (33.3%), and averting significant drug-drug interactions (10.4%). In patients anticipated to have a change in viral load (VL) as a result of the AST recommendations, we identified a significant benefit in virologic outcomes at 6 and 12 months when recommendations were implemented within 6 months of ARV review. Patients who had recommendations implemented within 6 months had a 7-fold higher probability of achieving a 0.7 log10 reduction in VL by 6 months, and this benefit remained significant after controlling for adherence.

CONCLUSIONS:

A systematic ARV stewardship program implemented at a pediatric HIV clinic significantly improved clinical outcomes. ARV stewardship programs can be considered a core strategy for continuous quality improvement in the management of HIV-infected children and adolescents.

Purchase full article at:   http://goo.gl/KZ9yEg

By:  Hsu AJ1, Neptune A, Adams C, Hutton N, Agwu AL.

• 1 The Johns Hopkins Hospital, Department of Pharmacy, Division of Pediatric Pharmacy, Baltimore, MD, USA 
• 2 Howard University College of Medicine, Washington, DC, USA 
• 3 Medical University of South Carolina, Charleston, SC, USA 
• 4 The Johns Hopkins University School of Medicine, Department of Pediatrics, Division of General Pediatrics & Adolescent Medicine, Baltimore, MD, USA 
• 5 The Johns Hopkins University School of Medicine, Department of Pediatrics, Division of Infectious Diseases, Baltimore, MD, USA.
• Pediatr Infect Dis J. 2016 Feb 19.  

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