Spatial distribution of incident pediatric Burkitt lymphoma in central and northern Malawi and association with malaria prevalence.

BACKGROUND: Burkitt lymphoma (BL) accounts for 90% of pediatric lymphomas in sub-Saharan Africa. Plasmodium falciparum malaria is considered an etiological factor of BL. We describe the geographic distribution of pediatric BL in Malawi and association with P. falciparum malaria prevalence rate (PfPR). METHODS: We enrolled 220 pathologically confirmed incident pediatric BL cases (2013-2018) into an observational clinical cohort at Kamuzu Central Hospital (KCH) in Lilongwe district. KCH is the main tertiary cancer referral center serving the central and northern regions of Malawi. Using an ecological study design, we calculated district-level annual BL incidence rate using census population estimates. District-level PfPR was extracted from the National Malaria Control Program 2010 report. BL incidence and PfPR maps were constructed in QGIS. Moran's I  test was used to identify BL spatial clusters. Pearson's correlation and multiple linear regression analyses were used to statistically examine the relationship between PfPR and BL. RESULTS: BL incidence was higher in central region districts (8.2 cases per million) than northern districts (2.9 cases per million) and was elevated in lakeshore districts. Districts with elevated PfPR tended to have elevated BL incidence. A low-risk BL cluster was detected in the north. Statistically, BL incidence was positively correlated with PfPR (r = .77, p < .01). A 1% increase in PfPR predicted an increase in BL incidence of 0.2 cases per million (p = .03), when controlling for travel time from referral district hospital to KCH. CONCLUSION: Our study supports evidence for an association between P. falciparum and BL and highlights a need to improve geographic accessibility to tertiary cancer services in Malawi's northern region.

The effect of azithromycin for management of HIV-associated chronic lung disease on right heart function: Results from the BREATHE trial.

BACKGROUND: Right heart abnormalities and pulmonary hypertension (PH) may be secondary to chronic lung disease. Chronic lung disease is common in children with HIV. In the BREATHE trial ( Trial registration: NCT02426112), azithromycin (AZM) reduced the risk of acute respiratory exacerbations in children aged 6-19 years with HIV-associated chronic lung disease (HCLD) taking antiretroviral therapy. We assessed the possible effect of AZM on right heart dysfunction and/or PH in the trial. METHODS: A standardised transthoracic echocardiogram using M-mode, two-dimensional and Doppler was performed, at baseline and at completion of weight-based AZM given weekly for 48 weeks. Linear regression was used to compare trial arms. RESULTS: A total of 169 participants (82 AZM arm; 87 placebo arm) were included. Participants in the placebo arm were older, median age 16.2 (13.0-18.2) vs 15.3 (12.9-17.4) years, p = 0.184 in the AZM arm. At baseline, right heart abnormalities (right ventricular systolic dysfunction (RVSD), dilatation, or PH) were observed in 7(4%). Following treatment, there was no difference in prevalence of RVSD between arms (p = 0.761). There was one incident case of suspected PH, and overall, no difference in pulmonary pressures. CONCLUSION: In children with HCLD, there was evidence of secondary cardiac effects, but AZM had no effect on right heart function. Long-term follow-up in children with HIV should be part of future research to understand the clinical implications of right heart abnormalities.

Impact of Maternal HIV Infection and Placental Malaria on the Transplacental Transfer of Influenza Antibodies in Mother-Infant Pairs in Malawi, 2013-2014.

BACKGROUND: Maternal influenza vaccination protects infants against influenza virus infection. Impaired transplacental transfer of influenza antibodies may reduce this protection. METHODS: We conducted a cross-sectional study of influenza vaccine-naïve pregnant women recruited at delivery from Blantyre (urban, low malaria transmission) and Chikwawa (rural, high malaria transmission) in Southern Malawi. HIV-infected mothers were excluded in Chikwawa. Maternal and cord blood antibodies against circulating influenza strains A/California/7/2009, A/Victoria/361/2011, B/Brisbane/60/2008, and B/Wisconsin/1/2010 were measured by hemagglutination inhibition (HAI). We studied the impact of maternal HIV infection and placental malaria on influenza antibody levels in mother-infant pairs in Blantyre and Chikwawa, respectively. RESULTS: We included 454 mother-infant pairs (Blantyre, n = 253; Chikwawa, n = 201). HIV-infected mothers and their infants had lower seropositivity (HAI titer ≥1:40) against influenza A(H1N1)pdm09 (mothers, 24.3 vs 45.4%; P = .02; infants, 24.3 vs 50.5%; P = .003) and A(H3N2) (mothers, 37.8% vs 63.9%; P = .003; infants, 43.2 vs 64.8%; P = .01), whereas placental malaria had an inconsistent effect on maternal and infant seropositivity. In multivariable analyses, maternal HIV infection was associated with reduced infant seropositivity (A(H1N1)pdm09: adjusted odds ratio [aOR], 0.34; 95% confidence interval [CI], 0.15-0.79; A(H3N2): aOR, 0.43; 95% CI, 0.21-0.89). Transplacental transfer was not impaired by maternal HIV or placental malaria. CONCLUSIONS: Maternal HIV infection influenced maternal antibody response to influenza A virus infection, and thereby antibody levels in newborns, but did not affect transplacental antibody transfer.

Epidemiology of Severe Acute Respiratory Illness and Risk Factors for Influenza Infection and Clinical Severity among Adults in Malawi, 2011-2013.

Data on the epidemiology of severe acute respiratory illness (SARI) in adults from low-income, high human immunodeficiency virus (HIV) prevalence African settings are scarce. We conducted adult SARI surveillance in Blantyre, Malawi. From January 2011 to December 2013, individuals aged ≥ 15 years with SARI (both inpatients and outpatients) were enrolled at a large teaching hospital in Blantyre, Malawi. Nasopharyngeal aspirates were tested for influenza and other respiratory viruses by polymerase chain reaction. We estimated hospital-attended influenza-positive SARI incidence rates and assessed factors associated with influenza positivity and clinical severity (Modified Early Warning Score > 4). We enrolled 1,126 SARI cases; 163 (14.5%) were positive for influenza. Human immunodeficiency virus prevalence was 50.3%. Annual incidence of hospital-attended influenza-associated SARI was 9.7-16.8 cases per 100,000 population. Human immunodeficiency virus was associated with a 5-fold greater incidence (incidence rate ratio 4.91, 95% confidence interval [CI]: 3.83-6.32). On multivariable analysis, female gender, as well as recruitment in hot, rainy season (December to March; adjusted odds ratios (aOR): 2.82, 95% CI: 1.57-5.06) and cool, dry season (April to August; aOR: 2.47, 95% CI: 1.35-4.15), was associated with influenza positivity, whereas influenza-positive patients were less likely to be HIV-infected (aOR: 0.59, 95% CI: 0.43-0.80) or have viral coinfection (aOR: 0.51, 95% CI: 0.36-0.73). Human immunodeficiency virus infection (aOR: 1.86; 95% CI: 1.35-2.56) and recruitment in hot, rainy season (aOR: 4.98, 95% CI: 3.17-7.81) were independently associated with clinical severity. In this high HIV prevalence population, influenza was associated with nearly 15% of hospital-attended SARI. Human immunodeficiency virus infection is an important risk factor for clinical severity in all-cause and influenza-associated SARI. Expanded access to HIV testing and antiretroviral treatment, as well as targeted influenza vaccination, may reduce the burden of SARI in Malawi and other high HIV prevalence settings.

Age Related Patterns of Disease and Mortality in Hospitalised Adults in Malawi.

BACKGROUND: The epidemic of non-communicable diseases (NCDs) in low and middle income countries (LMICs) is widely recognised as the next major challenge to global health. However, in many LMICs, infectious diseases are still prevalent resulting in a "double burden" of disease. With increased life expectancy and longevity with HIV, older adults may particularly be at risk of this double burden. Here we describe the relative contributions of infections and NCDs to hospital admissions and mortality, according to age, in Malawi's largest hospital. METHODS: Primary diagnosis on discharge/death, mortality rates, and HIV status were recorded prospectively on consecutive adult medical in-patients over 2 years using an electronic medical records system. Diagnoses were classified as infections or NCDs and analysed according to age and gender. FINDINGS: 10,191 records were analysed. Overall, infectious diseases, particularly those associated with HIV, were the leading cause of admission. However, in adults ≥55 years, NCDs were the commonest diagnoses. In adults <55 years 71% of deaths were due to infections whereas in adults ≥55 years 56% of deaths were due to NCDs. INTERPRETATION: Infectious diseases are still the leading cause of adult admission to a central hospital in Malawi but in adults aged ≥55 years NCDs are the most frequent diagnoses. HIV was an underlying factor in the majority of adults with infections and was also present in 53% of those with NCDs. These findings highlight the need for further health sector shifts to address the double burden of infectious and NCDs, particularly in the ageing population.

Respiratory Virus-Associated Severe Acute Respiratory Illness and Viral Clustering in Malawian Children in a Setting With a High Prevalence of HIV Infection, Malaria, and Malnutrition.

BACKGROUND: We used data from 4 years of pediatric severe acute respiratory illness (SARI) sentinel surveillance in Blantyre, Malawi, to identify factors associated with clinical severity and coviral clustering. METHODS: From January 2011 to December 2014, 2363 children aged 3 months to 14 years presenting to the hospital with SARI were enrolled. Nasopharyngeal aspirates were tested for influenza virus and other respiratory viruses. We assessed risk factors for clinical severity and conducted clustering analysis to identify viral clusters in children with viral codetection. RESULTS: Hospital-attended influenza virus-positive SARI incidence was 2.0 cases per 10 000 children annually; it was highest among children aged <1 year (6.3 cases per 10 000), and human immunodeficiency virus (HIV)-infected children aged 5-9 years (6.0 cases per 10 000). A total of 605 SARI cases (26.8%) had warning signs, which were positively associated with HIV infection (adjusted risk ratio [aRR], 2.4; 95% confidence interval [CI], 1.4-3.9), respiratory syncytial virus infection (aRR, 1.9; 95% CI, 1.3-3.0) and rainy season (aRR, 2.4; 95% CI, 1.6-3.8). We identified 6 coviral clusters; 1 cluster was associated with SARI with warning signs. CONCLUSIONS: Influenza vaccination may benefit young children and HIV-infected children in this setting. Viral clustering may be associated with SARI severity; its assessment should be included in routine SARI surveillance.