Long-term outcomes for children and adolescents with Kaposi sarcoma.

OBJECTIVES: Kaposi sarcoma (KS) is one of the most common childhood cancers in eastern and central Africa. It has become a treatable disease with increasing availability of antiretroviral therapy (ART) and chemotherapy. We aimed to fill the data gap in establishing whether long-term survival is achievable for children in low-income countries. METHODS: We retrospectively analysed data for children and adolescents aged ≤ 18.9 years diagnosed with HIV-related or endemic KS from 2006 to 2015 who received standardized institutional treatment regimens utilizing chemotherapy plus ART (if HIV-positive) at a tertiary care public hospital in Lilongwe, Malawi. Long-term survival was analysed and mortality was associated with KS for those with refractory/progressive disease at the time of death. RESULTS: There were 207 children/adolescents with KS (90.8% HIV-related); 36.7% were alive, 54.6% had died, and 8.7% had been lost to follow-up. The median follow-up time for survivors was 6.9 years (range 4.2-13.9 years). Death occurred at a median of 5.3 months after KS diagnosis (range 0.1-123 months). KS progression was associated with mortality for most (61%) early deaths (survival time of < 6 months); conversely, KS was associated with a minority (31%) of late-onset deaths (after 24 months). The 7-year overall survival was 37% [95% confidence interval (CI) 30-44%] and was higher for those diagnosed between 2011 and 2015 compared to 2006-2010: 42% (95% CI 33-51%) versus 29% (95% CI 20-39%), respectively (P = 0.01). Among the 66 HIV-positive survivors, 58% were still on first-line ART. CONCLUSIONS: Long-term survival is possible for pediatric KS in low-resource settings. Despite better survival in more recent years, there remains room for improvement.

Kaposi Sarcoma Herpesvirus Inflammatory Cytokine Syndrome-like Clinical Presentation in Human Immunodeficiency Virus-infected Children in Malawi.

We describe 7 human immunodeficiency virus-infected Malawian children with Kaposi sarcoma who met criteria for Kaposi sarcoma herpesvirus (KSHV) inflammatory cytokine syndrome. Each presented with persistent fevers, bulky lymphadenopathy, massive hepatosplenomegaly, and severe cytopenias. Plasma analyses were performed in 2 patients, both demonstrating extreme elevations of KSHV viral load and interleukin 6.

KSHV viral load and Interleukin-6 in HIV-associated pediatric Kaposi sarcoma-Exploring the role of lytic activation in driving the unique clinical features seen in endemic regions.

Kaposi sarcoma (KS) is among the most common childhood malignancies in central, eastern, and southern Africa. Although its unique clinical features have been established, biological mechanisms related to the causative agent, KS-associated herpes-virus (KSHV), have yet to be explored in children. We performed a prospective observational pilot study to explore associations between KSHV viral load (VL), human interleukin-6 (IL-6) and IL-10 levels, and clinical characteristics of 25 children with KS in Lilongwe, Malawi from June 2013-August 2015. The median age was 6.4 years. Lymphadenopathy was the most common site of KS involvement (64%), followed by skin and oral mucosa (44% each), woody edema (12%), and pulmonary (8%). Baseline samples for plasma KSHV VL, IL-6 and IL-10 analyses were available for 18/25 patients (72%) at time of KS diagnosis. KSHV VL was detectable at baseline in 12/18 (67%) patients, the median baseline IL-6 level was 8.53 pg/mL (range 4.31-28.33), and the median baseline IL-10 level was 19.53 pg/mL (range 6.91-419.69). Seven (39%) patients presented with an IL-6 level > 10 pg/mL (exceeding twice the upper limit of normal). Detectable KSHV VL was significantly associated with lymphadenopathic KS (p = 0.004), while having undetectable KSHV VL was associated with a higher likelihood of presenting with hyperpigmented skin lesions (p = 0.01). Detectable KSHV VL and elevated IL-6 levels are present in a subset of children with KS. Lytic activation of KSHV and associated elevation in KSHV VL may contribute to the unique clinical manifestations of pediatric KS in KSHV-endemic regions of Africa.

Importance of authorship and inappropriate authorship assignment in paediatric research in low- and middle-income countries.

OBJECTIVE: To understand the importance of authorship and authorship position, and gauge perceptions of inappropriate authorship assignment, among authors publishing paediatric research conducted in low- and middle-income countries (LMICs). METHODS: We conducted a cross-sectional, mixed-methods study using an online survey of both corresponding and randomly selected, non-corresponding authors who published research conducted in LMICs from 2006 to 2015 in the top four paediatric journals by Eigenfactor score. We used chi-square tests to compare responses by authors living in LMICs to authors living in high-income countries (HICs). We analysed qualitative responses using thematic analysis. RESULTS: Of 1420 potential respondents, 19.6% (n = 279) completed the survey. 57% (n = 159) lived in LMICs and 43% (n = 120) in HICs. LMIC authors more commonly perceived first authorship as most important for their academic advancement than HIC authors (74.2% vs. 60.8%, P = 0.017), while HIC authors reported last authorship as most important (25.1% vs. 38.3%, P = 0.018). 65% (n = 181) of respondents believed that their collaborators had been inappropriately assigned authorship positions (no difference in LMIC and HIC responses) and 32.6% (n = 91) reported personally accepting inappropriate authorship positions (more common in HIC respondents, P = 0.005). In qualitative data, respondents questioned the applicability of standard authorship guidelines for collaborative research conducted in LMICs. CONCLUSIONS: LMIC and HIC authors held different perceptions about the importance of authorship position. Reported inappropriate authorship assignment was common among both LMIC and HIC respondents. Alternatives to standard authorship criteria for research conducted in LMICs merit further studies.

OBJECTIF: Comprendre l'importance de la paternité d'auteur et de la position de l'auteur, et évaluer les perceptions de l'attribution inappropriée de la paternité d'auteur parmi les auteurs qui publient des recherches pédiatriques menées dans des pays à revenu faible ou intermédiaire (PRFI). MÉTHODES: Nous avons mené une étude transversale à méthodes mixtes avec un sondage en ligne auprès d'auteurs de correspondance et sélectionnés au hasard, d'auteurs not de correspondance, ayant publié des recherches menées dans des PRFIde 2006 à 2015 dans les quatre revues pédiatriques les mieux classées par le score d'Eigenfactor. Nous avons utilisé des tests de chi carré pour comparer les réponses des auteurs des PRFI à ceux des aux auteurs des pays à revenu élevé (PRE). Nous avons analysé les réponses qualitatives à l'aide d'une analyse thématique. RÉSULTATS: Sur 1.420 répondants potentiels, 19,6% (n = 279) ont répondu au sondage. 57% (n = 159) vivaient dans des PRFI et 43% (n = 120) dans des PRE. Les auteurs des PRFI estimaient plus souvent que la position de premier auteur était le plus important pour leur avancement universitaire que les auteurs des PRE (74,2% contre 60,8%, P = 0,017), tandis que les auteurs desPRE ont déclaré que le dernier auteur était le plus important (25,1% contre 38,3%, P = 0,018). 65% (n = 181) des répondants estimaient que des positions d'auteur avaient été attribués de manière inappropriée à leurs collaborateurs (aucune différence entre les réponses des PRFI et des PRE) et 32,6% (n = 91) ont déclaré avoir personnellement accepté des positions d'auteurs inappropriées (plus fréquents chez les répondants desPRE, P = 0,005). En ce qui concerne les données qualitatives, les répondants se sont interrogés sur l'applicabilité des directives standards en matière de paternité d'auteur pour la recherche collaborative menée dans les PRFI. CONCLUSIONS: Les auteurs des PRFI et desPREont des perceptions différentes sur l'importance de la position de l'auteur. L'attribution inappropriée de laposition d'auteur signalée était fréquente chez les répondants des PRFI et des PRE. Les alternatives aux critères standards de la paternité d'auteur pour les recherches menées dans les PRFI méritent d'être approfondies.

VITAL Start: Video-Based Intervention to Inspire Treatment Adherence for Life-Pilot of a Novel Video-Based Approach to HIV Counseling for Pregnant Women Living with HIV.

We developed and piloted a video-based intervention targeting HIV-positive pregnant women to optimize antiretroviral therapy (ART) retention and adherence by providing a VITAL Start (Video-intervention to Inspire Treatment Adherence for Life) before ART. VITAL Start (VS) was grounded in behavior-determinant models and developed through an iterative multi-stakeholder process. Of 306 pregnant women eligible for ART, 160 were randomized to standard of care (SOC), 146 to VS and followed for one-month. Of those assigned to VS, 100% completed video-viewing; 96.5% reported they would recommend VS. Of 11 health workers interviewed, 82% preferred VS over SOC; 91% found VS more time-efficient. Compared to SOC, VS group had greater change in HIV/ART knowledge (p < 0.01), trend towards being more likely to start ART (p = 0.07), and better self-reported adherence (p = 0.02). There were no significant group differences in 1-month retention and pharmacy pill count. VITAL Start was highly acceptable, feasible, with promising benefits to ART adherence.

The epidemiology of adolescents living with perinatally acquired HIV: A cross-region global cohort analysis.

BACKGROUND: Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in "real-life" settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. METHODS AND FINDINGS: Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5-5.2) years for the total cohort and 6.4 (3.6-8.0) years in Europe, 3.7 (2.0-5.4) years in North America, 2.5 (1.2-4.4) years in South and Southeast Asia, 5.0 (2.7-7.5) years in South America and the Caribbean, and 2.1 (0.9-3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3-2.1) years in North America to 7.1 (5.3-8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4-2.6) years in North America to 7.9 (6.0-9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%-2.8%), 15.6% (15.1%-16.0%), and 11.3% (10.9%-11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%-1.1%]) and highest in South America and the Caribbean (4.4% [3.1%-6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%-6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%-13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. CONCLUSION: To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses.

Translation, psychometric validation, and baseline results of the Patient-Reported Outcomes Measurement Information System (PROMIS) pediatric measures to assess health-related quality of life of patients with pediatric lymphoma in Malawi.

INTRODUCTION: Internationally validated tools to measure patient-reported health-related quality of life (HRQoL) are available, but efforts to translate and culturally validate such tools in sub-Saharan Africa (SSA) are scarce, particularly among children. METHODS: The Patient-Reported Outcomes Measurement Information System 25-item pediatric short form (PROMIS-25) assesses six HRQoL domains-mobility, anxiety, depression, fatigue, peer relationships, and pain interference-by asking four questions per domain. There is a single-item pain intensity item. The PROMIS-25 was translated into Chichewa and validated for use in Malawi using mixed qualitative and quantitative methods. The validity and reliability of the PROMIS-25 was assessed. RESULTS: Fifty-four pediatric patients with lymphoma completed the PROMIS-25. Structural validity was supported by interitem correlations and principal component analysis. Reliability of each scale was satisfactory (range alpha = 0.71-0.93). Known group validity testing showed that anemic children had worse fatigue (P = 0.016) and children with poor performance status had worse mobility (P < 0.001) and pain interference (P = 0.005). Compared to children with cancer in the United States, children from Malawi reported lower levels of mobility, higher anxiety, higher depressive symptoms, higher fatigue, better satisfaction with peer relationships, and higher pain interference. CONCLUSION: Translation and cultural validation of the PROMIS-25 into Chichewa for Malawi was successful. Baseline HRQoL for patients with pediatric lymphoma in Malawi is poor for all domains except peer relationships. This emphasizes an urgent need to address HRQoL among children undergoing cancer treatment in SSA using self-reported instruments validated within the local context.

Risk factors and reasons for treatment abandonment among children with lymphoma in Malawi.

PURPOSE: Lymphoma is the commonest pediatric cancer in sub-Saharan Africa (SSA). Frequent treatment abandonment contributes to suboptimal outcomes. We examined risk factors and reasons for treatment abandonment for this population in Malawi. METHODS: We conducted a mixed methods study among children < 18 years old with newly diagnosed lymphoma, prospectively enrolled during 2013-2016. All children received standardized diagnosis and treatment, and were followed for up to 2 years. Treatment abandonment was defined as failure to attend prescribed chemotherapy within 4 weeks, or post-treatment visit within 3 months. Child, guardian, and household characteristics associated with treatment abandonment were assessed. Semi-structured interviews were conducted with primary caregivers of children experiencing treatment abandonment. RESULTS: Of 121 children with newly diagnosed lymphoma, 72 (60%) had complete information regarding child, guardian, and household characteristics. Of these, 56 (78%) had Burkitt's and 16 (22%) Hodgkin's lymphoma. Forty-nine (68%) were male, median age was 10.6 years (interquartile range [IQR] 7.9-13.0), and 26 (36%) experienced treatment abandonment. Lack of guardian education and travel time ≥ 4 h to clinic were independently associated with treatment abandonment, with adjusted hazard ratio (aHR) 3.8 [95% confidence interval (CI) 1.5-8.9, p = 0.005] and aHR 2.9 (95% CI 1.2-6.9, p = 0.019), respectively. Commonest reasons for treatment abandonment endorsed by 15 guardians were community influence, suboptimal clinic environment, logistical challenges, transport costs, treatment toxicities, loss of hope, alternative healers, and beliefs about cure. CONCLUSIONS: These findings highlight families at risk for treatment abandonment, underlying reasons, and opportunities to improve retention in care for pediatric cancer patients in SSA.

Plasma Epstein-Barr virus DNA for pediatric Burkitt lymphoma diagnosis, prognosis and response assessment in Malawi.

Point-of-care tools are needed in sub-Saharan Africa (SSA) to improve pediatric Burkitt lymphoma (BL) diagnosis and treatment. We evaluated plasma Epstein-Barr virus (pEBV) DNA as a pediatric BL biomarker in Malawi. Prospectively enrolled children with BL were compared to classical Hodgkin lymphoma (cHL) and nonlymphoma diagnoses. Pediatric BL patients received standardized chemotherapy and supportive care. pEBV DNA was measured at baseline, mid-treatment, and treatment completion. Of 121 assessed children, pEBV DNA was detected in 76/88 (86%) with BL, 16/17 (94%) with cHL, and 2/16 (12%) with nonlymphoma, with proportions higher in BL versus nonlymphoma (p < 0.001) and similar in BL versus cHL (p = 0.69). If detected, median pEBV DNA was 6.1 log10 copies/mL for BL, 4.8 log10 copies/mL for cHL, and 3.4 log10 copies/mL for nonlymphoma, with higher levels in BL versus cHL (p = 0.029), and a trend toward higher levels in BL versus nonlymphoma (p = 0.062). pEBV DNA declined during treatment in the cohort overall and increased in several children before clinical relapse. Twelve-month overall survival was 40% in the cohort overall, and for children with baseline pEBV detected, survival was worse if baseline pEBV DNA was ≥6 log10 copies/mL versus <6 log10 copies/mL (p = 0.0002), and also if pEBV DNA was persistently detectable at mid-treatment versus undetectable (p = 0.041). Among children with baseline pEBV DNA detected, viremia was the only significant risk factor for death by 12 months in multivariate analyses (adjusted hazard ratio 1.35 per log10 copies/mL, 95% CI 1.04-1.75, p = 0.023). Quantitative pEBV DNA has potential utility for diagnosis, prognosis, and response assessment for pediatric BL in SSA.

Authorship in paediatric research conducted in low- and middle-income countries: parity or parasitism?

OBJECTIVES: Interest in global health has increased greatly in the past two decades. Concomitantly, the number and complexity of research partnerships between high-income (HIC) and low- and middle-income countries (LMICs) has grown. We aimed to determine whether there is authorship parity (equitable representation and author order) or parasitism (no authors from study countries) in paediatric research conducted in LMICs. METHODS: We reviewed all articles published from 2006 to 2015 in the four paediatric journals with the highest Eigenfactor scores. We limited our review to articles from LMICs and abstracted information on author affiliation and order, funding source and study design. We calculated Student's t-tests and chi-square using Fisher's exact test with Monte Carlo estimates. RESULTS: There were 24 169 articles published during the study period, and 1243 met inclusion criteria. Of those, 95.9% (n = 1,192) included at least one author affiliated with a LMIC. Among multicountry studies (n = 165), 40.4% did not include authors from every LMIC involved. Of the 9876 authors, most were affiliated with institutions from upper-middle-income countries (41.7%) and HICs (32.7%), with far fewer affiliated with lower middle-income (15.5%) and low-income countries (5.4%) (P < 0.001). In articles from low-income countries, first and last authors from HICs were more common than authors with low-income country affiliations (P < 0.001). CONCLUSIONS: Authorship parasitism was rare overall but common in multicountry studies. In studies conducted in low-income countries, HIC authors more commonly occupied first and last author positions than authors from the study countries. Where LMIC authors make substantial contributions, researchers should strive for authorship parity.

Index case finding facilitates identification and linkage to care of children and young persons living with HIV/AIDS in Malawi.

OBJECTIVES: Evaluation of a novel index case finding and linkage-to-care programme to identify and link HIV-infected children (1-15 years) and young persons (>15-24 years) to care. METHODS: HIV-infected patients enrolled in HIV services were screened and those who reported untested household members (index cases) were offered home- or facility-based HIV testing and counselling (HTC) of their household by a community health worker (CHW). HIV-infected household members identified were enrolled in a follow-up programme offering home and facility-based follow-up by CHWs. RESULTS: Of the 1567 patients enrolled in HIV services, 1030 (65.7%) were screened and 461 (44.8%) identified as index cases; 93.5% consented to HIV testing of their households and of those, 279 (64.7%) reported an untested child or young person. CHWs tested 711 children and young persons, newly diagnosed 28 HIV-infected persons (yield 4.0%; 95% CI: 2.7-5.6), and identified an additional two HIV-infected persons not enrolled in care. Of the 30 HIV-infected persons identified, 23 (76.6%) were linked to HIV services; 18 of the 20 eligible for ART (90.0%) were initiated. Median time (IQR) from identification to enrolment into HIV services was 4 days (1-8) and from identification to ART start was 6 days (1-8). CONCLUSIONS: Almost half of HIV-infected patients enrolled in treatment services had untested household members, many of whom were children and young persons. Index case finding, coupled with home-based testing and tracked follow-up, is acceptable, feasible and facilitates the identification and timely linkage to care of HIV-infected children and young persons.

Task shifting to clinical officer-led echocardiography screening for detecting rheumatic heart disease in Malawi, Africa.

BACKGROUND: Echocardiographic screening for rheumatic heart disease in asymptomatic children may result in early diagnosis and prevent progression. Physician-led screening is not feasible in Malawi. Task shifting to mid-level providers such as clinical officers may enable more widespread screening. Hypothesis With short-course training, clinical officers can accurately screen for rheumatic heart disease using focussed echocardiography. METHODS: A total of eight clinical officers completed three half-days of didactics and 2 days of hands-on echocardiography training. Clinical officers were evaluated by performing screening echocardiograms on 20 children with known rheumatic heart disease status. They indicated whether children should be referred for follow-up. Referral was indicated if mitral regurgitation measured more than 1.5 cm or there was any measurable aortic regurgitation. The κ statistic was calculated to measure referral agreement with a paediatric cardiologist. Sensitivity and specificity were estimated using a generalised linear mixed model, and were calculated on the basis of World Heart Federation diagnostic criteria. RESULTS: The mean κ statistic comparing clinical officer referrals with the paediatric cardiologist was 0.72 (95% confidence interval: 0.62, 0.82). The κ value ranged from a minimum of 0.57 to a maximum of 0.90. For rheumatic heart disease diagnosis, sensitivity was 0.91 (95% confidence interval: 0.86, 0.95) and specificity was 0.65 (95% confidence interval: 0.57, 0.72). CONCLUSION: There was substantial agreement between clinical officers and paediatric cardiologists on whether to refer. Clinical officers had a high sensitivity in detecting rheumatic heart disease. With short-course training, clinical officer-led echo screening for rheumatic heart disease is a viable alternative to physician-led screening in resource-limited settings.

Identifying opportunities to bridge disparity gaps in curing childhood cancer in Malawi: Malignancies with excellent curative potential account for the majority of diagnoses.

The majority of African children with cancer die without access to resources. We describe efforts to build a public treatment program with curative intent for childhood cancer in Lilongwe, Malawi despite severe limitations in diagnostic and therapeutic resources. We retrospectively analyzed a cohort of childhood cancer patients at Kamuzu Central Hospital from 12/2011-6/2013. Consistently available chemotherapeutic agents were limited to cyclophosphamide, vincristine, doxorubicin, bleomycin, methotrexate, and prednisone. Of 258 newly diagnosed childhood malignancies, 17 patients with retinoblastoma were excluded from clinical analyses due to insufficient clinical data. Among the remainder of the cohort (n = 241), 42% were female with median age 8.4 years (range 0.6-17.9). Forty-six (19%) were HIV-infected (42 Kaposi sarcoma, 3 Burkitt lymphoma, 1 Hodgkin lymphoma). The most common clinical presentations were palpable abdominal mass (41%), peripheral lymphadenopathy (33%), and jaw mass (17%). Nearly two-thirds of total diagnoses were accounted for by Burkitt lymphoma (n = 74), Kaposi sarcoma (n = 52), Hodgkin lymphoma (n = 21), and Wilms tumor (n = 19). Twelve-month overall survival for these 4 most common diagnoses was 54% (95% confidence interval 46-61) versus 19% (95% confidence interval 11-30) for all other diagnoses (median follow-up 19 months). Treatment-related mortality was highest in patients with non-Wilms solid tumors of the abdomen (48% versus 10% for the overall cohort, p < 0.001), while treatment abandonment was highest in patients with bone and soft-tissue sarcomas (29% versus 14% overall, p = 0.05). Childhood cancers with excellent curative potential accounted for the majority of patients, establishing an opportunity to build treatment programs with curative intent despite severe limitations.

Lost opportunities to identify and treat HIV-positive patients: results from a baseline assessment of provider-initiated HIV testing and counselling (PITC) in Malawi.

OBJECTIVE: To assess implementation of provider-initiated testing and counselling (PITC) for HIV in Malawi. METHODS: A review of PITC practices within 118 departments in 12 Ministry of Health (MoH) facilities across Malawi was conducted. Information on PITC practices was collected via a health facility survey. Data describing patient visits and HIV tests were abstracted from routinely collected programme data. RESULTS: Reported PITC practices were highly variable. Most providers practiced symptom-based PITC. Antenatal clinics and maternity wards reported widespread use of routine opt-out PITC. In 2014, there was approximately 1 HIV test for every 15 clinic visits. HIV status was ascertained in 94.3% (5293/5615) of patients at tuberculosis clinics, 92.6% (30,675/33,142) of patients at antenatal clinics and 49.4% (6871/13,914) of patients at sexually transmitted infection clinics. Reported challenges to delivering PITC included test kit shortages (71/71 providers), insufficient physical space (58/71) and inadequate number of HIV counsellors (32/71) while providers from inpatient units cited the inability to test on weekends. CONCLUSIONS: Various models of PITC currently exist at MoH facilities in Malawi. Only antenatal and maternity clinics demonstrated high rates of routine opt-out PITC. The low ratio of facility visits to HIV tests suggests missed opportunities for HIV testing. However, the high proportion of patients at TB and antenatal clinics with known HIV status suggests that routine PITC is feasible. These results underscore the need to develop clear, standardised PITC policy and protocols, and to address obstacles of limited health commodities, infrastructure and human resources.

Hospital admissions from a pediatric HIV care and treatment program in Malawi.

BACKGROUND: The scale up of pediatric antiretroviral treatment programs across Sub-Saharan Africa over the last decade has brought increasing numbers of children into HIV care. This patient population requiring life-long care presents new challenges in the outpatient and inpatient settings. We sought to describe hospitalizations from a large pediatric HIV treatment facility to better understand the scope of the situation and identify areas for improved care delivery. METHODS: We conducted a retrospective case series of all HIV-infected and exposed patients <18 years enrolled at Baylor College of Medicine Children's Foundation Malawi, from October 2004-October 2010. Patients admitted to the hospital on or after the day of enrollment were included. Data were extracted from electronic clinic records. Analysis was done at the patient and admission level, as some patients had multiple admissions. RESULTS: Of 5062 patients enrolled in care, 877 (17.3 %) had 1137 admissions at median age 24 months (IQR: 12-62). 191 (21.8 %) patients had multiple admissions. A high proportion of admissions occurred in patients under two years (49.4 %), those within one month of clinic enrollment (32.9 %), those with severe immune suppression (44.0 %), and those not on ART (48.5 %). The frequency of primary admission diagnoses varied across these same variables, with malnutrition, pneumonia, and malaria being the most common. CONCLUSIONS: Illness requiring hospitalization is common in HIV-infected and exposed children and these results reinforce the need for a comprehensive care package with special attention to nutrition. Strengthened programs for malaria prevention and expanded access to pneumococcal vaccine are also needed. The high burden of admissions in children under 24 months and those newly enrolled in care suggests a need for continued improvement of early infant diagnosis and provider-initiated testing programs to link patients to care before they are symptomatic. Similarly, the high proportion of admissions in those not yet started on ART emphasizes the importance of rapid initiation of ART for eligible pediatric patients.

Seroprevalence of CMV, HSV-2 and HBV among HIV-Infected Malawian Children: A Cross-sectional Survey.

BACKGROUND: Little is known about viral co-infections in African human immunodeficiency virus (HIV)-infected children. We examined the prevalence of seromarkers for cytomegalovirus (CMV), herpes simplex virus type 2 (HSV-2) and hepatitis B virus (HBV) infections among HIV-infected, antiretroviral treatment (ART)-naïve children in Lilongwe, Malawi. METHODS: Ninety-one serum samples were tested for IgG and IgM antibodies to CMV, and IgG antibodies to HSV-2 and hepatitis B surface antigen (HBsAg). Baseline demographic, clinical and laboratory data were abstracted from electronic records. RESULTS: CMV IgG was the most common positive result in all age groups (in 73% of children <1 year, and 100% in all other groups). Three patients were CMV IgM positive (3.3%), suggesting acute infection. HSV-2 IgG was positive in four patients (4.4%), and HBsAg in two (2.2%). CONCLUSIONS: CMV infection occurred early in life, and few children had specific signs of CMV infection at the time of ART initiation. Unrecognized HBV infection represents opportunities for testing and treatment of HIV/HBV co-infected children.

Factors associated with depression among adolescents living with HIV in Malawi.

BACKGROUND: Prior research suggests that a high prevalence of depression, with a detrimental impact on treatment outcomes exists among HIV-infected youth. Data on potential risk factors of depression among HIV-infected youth in sub-Saharan Africa are scarce. This cross-sectional study aimed to identify contributory/protective factors associated with depression in Malawian adolescents 12-18 years old living with HIV. METHODS: Depression was measured by a validated Chichewa version of the Beck Depression Inventory version-II (BDI-II) and the Children's Depression Rating Scale-Revised (CDRS-R). Data on variables thought to potentially be contributory/protective were collected and included: socio-demographics, past traumatic events/stressors, behavioural factors/social support, and bio-clinical parameters. Chi-square test or two-sample t-test was used to explore associations between factors and depression. Additional testing via linear/logistic regression, adjusting for age and sex, identified candidate variables (p < 0.1). Final regression models included variables with significant main effects and interactions. RESULTS: Of the 562 participants enrolled (mean age, 14.5 years [SD 2.0]; 56.1% female), the prevalence of depression was 18.9%. In multivariate linear regression, the variables significantly associated with higher BDI-II score were female gender, fewer years of schooling, death in the family/household, failing a school term/class, having a boyfriend/girlfriend, not disclosed or not having shared one's HIV status with someone else, more severe immunosuppression, and bullied for taking medications. Bullying victimization was reported by 11.6% of respondents. We found significant interactions: older participants with lower height-for-age z-scores and dissatisfied with their physical appearance had higher BDI-II scores. In multivariate logistic regression, factors significantly associated with depression were: older age, OR 1.23 (95% CI 1.07-1.42); fewer years of schooling, OR 3.30 (95% CI 1.54-7.05); and bullied for taking medications, (OR 4.20 (95% CI 2.29-7.69). CONCLUSION: Having fewer years of schooling and being bullied for taking medications were most clearly associated with depression. Programmes to support the mental health needs of HIV-infected adolescents that address issues such as disclosure, educational support, and, most notably, bullying may improve treatment outcomes and are recommended.

Effect of women's groups and volunteer peer counselling on rates of mortality, morbidity, and health behaviours in mothers and children in rural Malawi (MaiMwana): a factorial, cluster-randomised controlled trial.

BACKGROUND: Women's groups and health education by peer counsellors can improve the health of mothers and children. We assessed their effects on mortality and breastfeeding rates in rural Malawi. METHODS: We did a 2×2 factorial, cluster-randomised trial in 185,888 people in Mchinji district. 48 equal-sized clusters were randomly allocated to four groups with a computer-generated number sequence. 24 facilitators guided groups through a community action cycle to tackle maternal and child health problems. 72 trained volunteer peer counsellors made home visits at five timepoints during pregnancy and after birth to support breastfeeding and infant care. Primary outcomes for the women's group intervention were maternal, perinatal, neonatal, and infant mortality rates (MMR, PMR, NMR, and IMR, respectively); and for the peer counselling were IMR and exclusive breastfeeding (EBF) rates. Analysis was by intention to treat. The trial is registered as ISRCTN06477126. FINDINGS: We monitored outcomes of 26,262 births between 2005 and 2009. In a factorial model adjusted only for clustering and the volunteer peer counselling intervention, in women's group areas, for years 2 and 3, we noted non-significant decreases in NMR (odds ratio 0.93, 0.64-1.35) and MMR (0.54, 0.28-1.04). After adjustment for parity, socioeconomic quintile, and baseline measures, effects were larger for NMR (0.85, 0.59-1.22) and MMR (0.48, 0.26-0.91). Because of the interaction between the two interventions, a stratified analysis was done. For women's groups, in adjusted analyses, MMR fell by 74% (0.26, 0.10-0.70), and NMR by 41% (0.59, 0.40-0.86) in areas with no peer counsellors, but there was no effect in areas with counsellors (1.09, 0.40-2.98, and 1.38, 0.75-2.54). Factorial analysis for the peer counselling intervention for years 1-3 showed a fall in IMR of 18% (0.82, 0.67-1.00) and an improvement in EBF rates (2.42, 1.48-3.96). The results of the stratified, adjusted analysis showed a 36% reduction in IMR (0.64, 0.48-0.85) but no effect on EBF (1.18, 0.63-2.25) in areas without women's groups, and in areas with women's groups there was no effect on IMR (1.05, 0.82-1.36) and an increase in EBF (5.02, 2.67-9.44). The cost of women's groups was US$114 per year of life lost (YLL) averted and that of peer counsellors was $33 per YLL averted, using stratified data from single intervention comparisons. INTERPRETATION: Community mobilisation through women's groups and volunteer peer counsellor health education are methods to improve maternal and child health outcomes in poor rural populations in Africa. FUNDING: Saving Newborn Lives, UK Department for International Development, and Wellcome Trust.

Meeting the challenge of hematologic malignancies in sub-Saharan Africa.

Cancer is a leading cause of death and disability in sub-Saharan Africa and will eclipse infectious diseases within the next several decades if current trends continue. Hematologic malignancies, including non-Hodgkin lymphoma, leukemia, Hodgkin lymphoma, and multiple myeloma, account for nearly 10% of the overall cancer burden in the region, and the incidence of non-Hodgkin lymphoma and Hodgkin lymphoma is rapidly increasing as a result of HIV. Despite an increasing burden, mechanisms for diagnosing, treating, and palliating malignant hematologic disorders are inadequate. In this review, we describe the scope of the problem, including the impact of endemic infections, such as HIV, Epstein-Barr virus, malaria, and Kaposi sarcoma-associated herpesvirus. We additionally describe current limitations in hematopathology, chemotherapy, radiotherapy, hematopoietic stem cell transplantation, and supportive care and palliation. We review contemporary treatment and outcomes of hematologic malignancies in the region and outline a clinical service and research agenda, which builds on recent global health successes combating HIV and other infectious diseases. Achieving similar progress against hematologic cancers in sub-Saharan Africa will require the sustained collaboration and advocacy of the entire global cancer community.

CD4 count outperforms World Health Organization clinical algorithm for point-of-care HIV diagnosis among hospitalised HIV-exposed Malawian infants.

OBJECTIVE: To determine, for the WHO algorithm for point-of-care diagnosis of HIV infection, the agreement levels between paediatricians and non-physician clinicians, and to compare sensitivity and specificity profiles of the WHO algorithm and different CD4 thresholds against HIV PCR testing in hospitalised Malawian infants. METHODS: In 2011, hospitalised HIV-exposed infants <12 months in Lilongwe, Malawi, were evaluated independently with the WHO algorithm by both a paediatrician and clinical officer. Blood was collected for CD4 and molecular HIV testing (DNA or RNA PCR). Using molecular testing as the reference, sensitivity, specificity and positive predictive value (PPV) were determined for the WHO algorithm and CD4 count thresholds of 1500 and 2000 cells/mm(3) by paediatricians and clinical officers. RESULTS: We enrolled 166 infants (50% female, 34% <2 months, 37% HIV infected). Sensitivity was higher using CD4 thresholds (<1500, 80%; <2000, 95%) than with the algorithm (physicians, 57%; clinical officers, 71%). Specificity was comparable for CD4 thresholds (<1500, 68%, <2000, 50%) and the algorithm (paediatricians, 55%, clinical officers, 50%). The positive predictive values were slightly better using CD4 thresholds (<1500, 59%, <2000, 52%) than the algorithm (paediatricians, 43%, clinical officers 45%) at this prevalence. CONCLUSION: Performance by the WHO algorithm and CD4 thresholds resulted in many misclassifications. Point-of-care CD4 thresholds of <1500 cells/mm(3) or <2000 cells/mm(3) could identify more HIV-infected infants with fewer false positives than the algorithm. However, a point-of-care option with better performance characteristics is needed for accurate, timely HIV diagnosis.