In-hospital mortality risk stratification in children aged under 5 years with pneumonia with or without pulse oximetry: A secondary analysis of the Pneumonia REsearch Partnership to Assess WHO REcommendations (PREPARE) dataset.

OBJECTIVES: We determined the pulse oximetry benefit in pediatric pneumonia mortality risk stratification and chest-indrawing pneumonia in-hospital mortality risk factors. METHODS: We report the characteristics and in-hospital pneumonia-related mortality of children aged 2-59 months who were included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest-indrawing pneumonia to identify mortality risk factors. RESULTS: Among 285,839 children, 164,244 (57.5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5.8%, 95% confidence interval [CI] 5.6-5.9% vs 2.1%, 95% CI 1.9-2.4%). One in five children with chest-indrawing pneumonia was hypoxemic (19.7%, 95% CI 19.0-20.4%), and the hypoxemic CFR was 10.3% (95% CI 9.1-11.5%). Other mortality risk factors were younger age (either 2-5 months [adjusted odds ratio (aOR) 9.94, 95% CI 6.67-14.84] or 6-11 months [aOR 2.67, 95% CI 1.71-4.16]), moderate malnutrition (aOR 2.41, 95% CI 1.87-3.09), and female sex (aOR 1.82, 95% CI 1.43-2.32). CONCLUSION: Children with a pulse oximetry measurement had a lower CFR. Many children hospitalized with chest-indrawing pneumonia were hypoxemic and one in 10 died. Young age and moderate malnutrition were risk factors for in-hospital chest-indrawing pneumonia-related mortality. Pulse oximetry should be integrated in pneumonia hospital care for children under 5 years.

Assembling a global database of child pneumonia studies to inform WHO pneumonia management algorithm: Methodology and applications.

Background: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines. Methods: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to share individual-level patient data. We collected data on demographic information, general medical history, and current illness episode, including history, clinical presentation, chest radiograph findings when available, treatment, and outcome. Data were gathered separately from hospital-based and community-based cases. We performed a narrative synthesis to describe the final data set. Results: Forty-one separate data sets were included in the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) database, 26 of which were hospital-based and 15 were community-based. The PREPARE database includes 285 839 children with pneumonia (244 323 in the hospital and 41 516 in the community), with detailed descriptions of clinical presentation, clinical progression, and outcome. Of 9185 pneumonia-related deaths, 6836 (74%) occurred in children <1 year of age and 1317 (14%) in children aged 1-2 years. Of the 285 839 episodes, 280 998 occurred in children 0-59 months old, of which 129 584 (46%) were 2-11 months of age and 152 730 (54%) were males. Conclusions: This data set could identify an improved specific, sensitive set of criteria for diagnosing clinical pneumonia and help identify sick children in need of referral to a higher level of care or a change of therapy. Field studies could be designed based on insights from PREPARE analyses to validate a potential revised pneumonia algorithm. The PREPARE methodology can also act as a model for disease database assembly.

An outbreak of infection due to severe acute respiratory corona virus-2 in a neonatal unit from a low and middle income setting.

Introduction: The provision of kangaroo mother care (KMC) involving continuous skin-to-skin care (SSC) is an important intervention in neonatal care, which is recommended even when women are infected with severe acute respiratory syndrome coronavirus (SARS-CoV-2). We report on a nosocomial outbreak of SARS-CoV-2 infections in a KMC ward. Methods: Contact tracing was conducted following the diagnosis of SARS-CoV-2 in a mother lodging in the KMC ward. All mother-newborn dyads in the KMC and healthcare workers (HCW) were tested for SARS-CoV-2 within 24-72 h of diagnosing the index case. Nasopharyngeal swab samples were obtained and tested from contacts, with a nucleic acid amplification test (NAAT) assay. Next-generation sequencing was done on positive samples. The secondary attack rate (SAR) was calculated assuming that the mother who presented with symptoms was the source of infection. Results: Twelve (70.6%) of 17 mothers and 8 (42.1%) of 19 neonates who were in the KMC ward with the index case were found to be positive with SARS-CoV-2. Seven (87.5%) of the 8 neonates who tested positive had mothers who also tested positive. Seventy-five percent (9/12) of the mothers and 62.5% (5/8) of the neonates who tested positive were asymptomatic. Eight (27.6%) of 29 HCW were found to be positive and were all asymptomatic. One neonate died from Acinetobacter baumannii sepsis, and his post-mortem lung histopathology showed features compatible with SARS-CoV-2 pneumonia. The sequencing of 13 specimens, which included 1 mother-newborn dyad, indicated clustering to the same phylogenetic lineage with identical mutations. In assessing for factors contributing to this outbreak, it was found that spaces between beds were less than 1 m and mothers had their meals around the same table at the same time. Conclusion: We report on a nosocomial outbreak of SARS-CoV-2 in a KMC ward, affecting a high number of mothers and neonates, and to a lesser extent HCWs. Although it is difficult to point to the index case as the source of this outbreak, as asymptomatic individuals can spread infection, the inadequate adherence to non-pharmaceutical interventions was assessed to have contributed to the spread of infection. This highlights the need for awareness and adherence to mitigation strategies to avoid SARS-CoV-2 outbreaks.

Derivation and validation of a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality in 20 countries.

INTRODUCTION: Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings. METHODS: We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for each candidate variable and assigned weighted points to derive the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) risk assessment tool. We used bootstrapped selection with 200 repetitions to internally validate the PREPARE risk assessment tool. RESULTS: A total of 27 388 children were included in the analysis (mean age 14.0 months, pneumonia-related case fatality ratio 3.1%). The PREPARE risk assessment tool included patient age, sex, weight-for-age z-score, body temperature, respiratory rate, unconsciousness or decreased level of consciousness, convulsions, cyanosis and hypoxaemia at baseline. The PREPARE risk assessment tool had good discriminatory value when internally validated (area under the curve 0.83, 95% CI 0.81 to 0.84). CONCLUSIONS: The PREPARE risk assessment tool had good discriminatory ability for identifying children at risk of hospitalised pneumonia-related mortality in a large, geographically diverse dataset. After external validation, this tool may be implemented in various settings to identify children at risk of hospitalised pneumonia-related mortality.

External validation of the RISC, RISC-Malawi, and PERCH clinical prediction rules to identify risk of death in children hospitalized with pneumonia.

BACKGROUND: Existing scores to identify children at risk of hospitalized pneumonia-related mortality lack broad external validation. Our objective was to externally validate three such risk scores. METHODS: We applied the Respiratory Index of Severity in Children (RISC) for HIV-negative children, the RISC-Malawi, and the Pneumonia Etiology Research for Child Health (PERCH) scores to hospitalized children in the Pneumonia REsearch Partnerships to Assess WHO REcommendations (PREPARE) data set. The PREPARE data set includes pooled data from 41 studies on pediatric pneumonia from across the world. We calculated test characteristics and the area under the curve (AUC) for each of these clinical prediction rules. RESULTS: The RISC score for HIV-negative children was applied to 3574 children 0-24 months and demonstrated poor discriminatory ability (AUC = 0.66, 95% confidence interval (CI) = 0.58-0.73) in the identification of children at risk of hospitalized pneumonia-related mortality. The RISC-Malawi score had fair discriminatory value (AUC = 0.75, 95% CI = 0.74-0.77) among 17 864 children 2-59 months. The PERCH score was applied to 732 children 1-59 months and also demonstrated poor discriminatory value (AUC = 0.55, 95% CI = 0.37-0.73). CONCLUSIONS: In a large external application of the RISC, RISC-Malawi, and PERCH scores, a substantial number of children were misclassified for their risk of hospitalized pneumonia-related mortality. Although pneumonia risk scores have performed well among the cohorts in which they were derived, their performance diminished when externally applied. A generalizable risk assessment tool with higher sensitivity and specificity to identify children at risk of hospitalized pneumonia-related mortality may be needed. Such a generalizable risk assessment tool would need context-specific validation prior to implementation in that setting.

Burden of Tuberculosis in South African Children During Treatment for Underlying Malignancies: A Single-center Experience in Johannesburg.

BACKGROUND: Children with cancer are immunocompromised with increased susceptibility to infections. We evaluated the burden of tuberculosis in children with cancer. METHODS: Children with cancer were enrolled and screened for Mycobacterium tuberculosis infection using the tuberculin skin test and enzyme-linked immune absorbent spot (T-SPOT.TB; Oxford Immunotec Ltd, Oxford, United Kingdom). Children with physician-suspected tuberculosis were investigated for M. tuberculosis using microscopy and culture on sputum or gastric washings. RESULTS: We enrolled 169 children; 10.7% were living with HIV. The tuberculin skin test was positive in 2.9% of patients, who were treated for tuberculosis and excluded from further analysis. The enzyme-linked immune absorbent spot (T-SPOT.TB) was either negative or indeterminate in the first 100 children screened. The incidence of tuberculosis was 7.6 per 100 child-years; 35.3% were culture-confirmed. Tuberculosis was diagnosed at a mean of 5.5 months from cancer diagnosis. A greater proportion of children living with HIV (44.4%) developed tuberculosis than those without (17.2%; adjusted P = 0.042). Children treated for high-risk acute lymphoblastic leukemia, advanced stage non-Hodgkin lymphoma and acute myeloid leukemia (P = 0.009) and those with a higher exposure-period (per 100 child-years) to corticosteroids courses (350 vs. 29.4; P < 0.001) had a higher incidence of tuberculosis. Twenty-six of 34 children (76.5%) with tuberculosis died; multiple infections were identified at the time of death. CONCLUSIONS: Screening children for tuberculosis infection at cancer diagnosis was of limited value. The high rate of tuberculosis and poor outcomes emphasize the need for a high index of suspicion to diagnose tuberculosis and consideration for antituberculosis treatment, especially for those with identified risk factors.

High Burden of Serious Bacterial Infections in African Children Treated for Cancer.

BACKGROUND: Infections in children treated for cancer contribute to morbidity and mortality. There is a paucity of studies on the incidence, etiology, risk factors and outcome of bacterial infections in African children treated for cancer. The aim of the study was to delineate the epidemiology of infectious morbidity and mortality in children with cancer. METHODS: The study enrolled children 1-19 years old with cancer and infections. Children were investigated for infection as part of standard of care. RESULTS: One hundred sixty-nine children were enrolled, 82 with hematologic malignancies and 87 with solid tumors and 10.7% were HIV infected. The incidence (per 100 child-years) of septic episodes (101) microbiologically confirmed (70.9) septic episodes, Gram-positive (48.5) and Gram-negative (37.6) sepsis was higher in children with hematologic malignancies than in those with solid tumors. The most common Gram-positive bacteria were Coagulase-negative Staphylococci, Streptococcus viridans and Enterococcus faecium, while the most common Gram-negative bacteria were Escherichia coli, Acinetobacter baumannii and Pseudomonas species. The C-reactive protein and procalcitonin was higher in microbiologically confirmed sepsis. The case fatality risk was 40.4%; 80% attributed to sepsis. The odds of dying from sepsis were higher in children with profound [adjusted odds ratio (aOR) = 3.96; P = 0.004] or prolonged neutropenia (aOR = 3.71; P = 0.011) and profound lymphopenia (aOR = 4.09; P = 0.003) and independently associated with pneumonia (53.85% vs. 29.23%; aOR = 2.38; P = 0.025) and tuberculosis (70.83% vs. 34.91%; aOR = 4.3; P = 0.005). CONCLUSION: The study emphasizes the high burden of sepsis in African children treated for cancer and highlights the association of tuberculosis and pneumonia as independent predictors of death in children with cancer.

Streptococcus pneumoniae colonization in pneumococcal vaccine-naïve human immunodeficiency virus-exposed infected and -uninfected South African children.

Pneumococcal nasopharyngeal colonization is a pre-requisite for pneumococcal disease; the risk for pneumococcal disease is high in children born to women living with human immunodeficiency virus (HIV). We investigated pneumococcal colonization, serotype distribution and antibiotic susceptibility of Streptococcus pneumoniae isolates carried by perinatal HIV-infected and HIV-exposed-uninfected (HEU) children.Serial nasopharyngeal swabs were collected from 331 HIV-infected and 491 HEU children, at up to 6 scheduled timepoints, between median ages of 25 to 181 weeks. Pneumococcus was identified by culture; serotyping and antibiotic susceptibility testing were done by conventional methods. No pneumococcal vaccine was given.HIV-infected children were less likely to be colonized with 7-valent pneumococcal conjugate vaccine 7 serotypes than HEU at a median of 25 weeks of age (23% vs 36%; P < .001); however, no differences in colonization between the 2 groups were observed at subsequent study-visits. Over the 36-months study-period pneumococcal colonization increased in both HIV-infected (from 45% to 77%) and HEU (from 57% to 61%) children. Over the study-period, pneumococcal isolates non-susceptible to cotrimoxazole decreased from 92% to 57% and had a similar trend to penicillin (from 65% to 42%) in HIV-infected children. Similarly, pneumococcal nonsusceptible to cotrimoxazole decreased from 93% to 57% and to penicillin from 69% to 37% in HEU children.Vaccine serotype colonization was common in this population and similar rates were observed in HIV-infected and HEU children. The prevalence of pneumococcal isolates non-susceptible to cotrimoxazole and penicillin decreased with age.

Vaccinology in sub-Saharan Africa.

We undertook a landscape analysis of vaccinology research and training in sub-Saharan Africa in order to identify key gaps and opportunities for capacity development in the field. We conducted interviews with regional and global immunisation experts, reviewed university and research centre websites, searched the scientific literature and analysed donor databases as part of our mapping exercise. We found that (1) few vaccinology training programmes are available in the region; (2) vaccinology research sites are numerous but unevenly distributed across countries and subregions and of widely varying capacity; (3) donor funding favours HIV, tuberculosis and malaria vaccine development over other high-burden diseases; (4) lack of vaccine design, manufacturing and regulatory capacity slows the progress of new vaccines through the research and development pipeline and (5) vaccine implementation research garners limited support. Regional efforts to strengthen African vaccinology expertise should develop advanced vaccinology training programmes, support clinical trial and implementation research sites in geographic areas with limited capacity and conduct multidisciplinary research to help design, license and roll out new vaccines.

Advocating for efforts to protect African children, families, and communities from the threat of infectious diseases: report of the First International African Vaccinology Conference.

One means of improving healthcare workers' knowledge of and attitudes to vaccines is through running vaccine conferences which are accessible, affordable, and relevant to their everyday work. Various vaccinology conferences are held each year worldwide. These meetings focus heavily on basic science with much discussion about new developments in vaccines, and relatively little coverage of policy, advocacy, and communication issues. A negligible proportion of delegates at these conferences come from Africa, home to almost 40% of the global burden of vaccine-preventable diseases. To the best of our knowledge, no major vaccinology conference has ever been held on the African continent apart from World Health Organization (WHO) meetings. The content of the first International African Vaccinology Conference was planned to be different; to focus on the science, with a major part of discussions being on clinical, programmatic, policy, and advocacy issues. The conference was held in Cape Town, South Africa, from 8 to 11 November 2012. The theme of the conference was "Advocating for efforts to protect African children, families, and communities from the threat of infectious diseases". There were more than 550 registered participants from 55 countries (including 37 African countries). There were nine pre-conference workshops, ten plenary sessions, and 150 oral and poster presentations. The conference discussed the challenges to universal immunisation in Africa as well as the promotion of dialogue and communication on immunisation among all stakeholders. There was general acknowledgment that giant strides have been made in Africa since the global launch of the Expanded Programme on Immunisation in 1974. For example, there has been significant progress in introducing new and under-utilised vaccines; including hepatitis B, Haemophilus influenza type b, pneumococcal conjugate, rotavirus, meningococcal A conjugate, and human papillomavirus vaccines. In May 2012, African countries endorsed the Global Vaccine Action Plan at the World Health Assembly. However, more than six million children remain incompletely vaccinated in Africa leading to more than one million vaccine-preventable deaths annually. In addition, there are persistent problems with leadership and planning, vaccine stock management, supply chain capacity and quality, provider-parent communication, and financial sustainability. The conference delegates agreed to move from talking to taking concrete actions around children's health, and to ensure that African governments commit to saving children's lives. They would advocate for lower costs of immunisation programmes in Africa, perhaps through bulk buying and improved administration of vaccine rollout through the New Partnership for Africa's Development.

Respiratory viral and pneumococcal coinfection of the respiratory tract: implications of pneumococcal vaccination.

The interactions between Streptococcus pneumoniae and other respiratory pathogens have been studied in vitro, in animal models and in humans - including epidemiologic and vaccine probe studies. Interactions of pneumococcus with respiratory viruses are common, and many mechanisms have been suggested to explain this phenomenon. The aim of this review is to explore pneumococcal interactions with respiratory viruses and consider the potential role that the pneumococcal polysaccharide-protein conjugate vaccine may play in modifying pneumococcal-respiratory viral interactions.

Antibiotic and systemic therapies for pneumonia in human immunodeficiency virus (HIV)-infected and HIV-exposed children.

INTRODUCTION: Pneumonia is the leading cause of mortality in both human immunodeficiency virus (HIV)-infected and HIV-exposed children. Administration of appropriate empirical antimicrobial and/or adjunctive systemic therapies may improve clinical outcomes. METHODOLOGY: To identify effective antimicrobial and/or adjunctive systemic therapy for pneumonia in HIV-infected and HIV-exposed, uninfected children, we searched for published and unpublished studies from 11 databases including MedLine, Global Health Database, Biological Abstracts (BIOSIS), the Cochrane Central Register of Controlled Trials, the World Health Organization Library Information System, AIDSLine, and the System for Information on Grey Literature in Europe, along with additional four regional databases including African Index Medicus, Latin America and Caribbean, Eastern Mediterranean, and South-East Asian databases. Data from full articles of selected studies were independently extracted by two reviewers. RESULTS: No a priori planned randomized controlled trials (RCT) were identified, only subgroup analyses of an RCT comparing oral amoxicillin versus parenteral penicillin for severe pneumonia in children. HIV-infected children had significantly higher treatment failure rates compared to their uninfected counterparts. An RCT study investigating adjunctive corticosteroid therapy for Pneumocystis jiroveci pneumonia (PCP) failed to identify a statistically significant reduction in mortality in the treatment group with a relative risk of 0.57 (95% CI 0.30-1.07). A before-after observational study showed substantial beneficial effect of corticosteroid treatment in reducing mortality among HIV-infected children with PCP. CONCLUSIONS: Insufficient evidence exists to identify effective antimicrobial treatment regimens for HIV-associated pneumonia in paediatric populations or confirm the beneficial effect of corticosteroid treatment for HIV-infected children with PCP.

Immunogenicity and safety of an acellular pertussis, diphtheria, tetanus, inactivated poliovirus, Hib-conjugate combined vaccine (Pentaxim) and monovalent hepatitis B vaccine at 6, 10 and 14 weeks of age in infants in South Africa.

OBJECTIVE: To assess the immunogenicity and safety data for a pentavalent combination vaccine containing acellular pertussis, inactivated poliovirus, and Haemophilus influenzae (Hib) polysaccharide-conjugate antigens. METHODS: A DTaP-IPV//PRP T vaccine (Pentaxim) was given at 6, 10 and 14 weeks of age to 212 infants in South Africa. Monovalent hepatitis B vaccine was given concomitantly. Immunogenicity was assessed using seroprotection and seroconversion rates; safety was assessed by monitoring for solicited injection site and systemic adverse events, and follow-up monitoring for unsolicited adverse events and serious adverse events. RESULTS: Immunogenicity was high for each vaccine antigen, and similar to a reference study done in France using a similar (2, 3 and 4 months of age) administration schedule. After the third dose, 94.6% of participants had anti-PRP > or = 0.15 microg/ml. The anti-PRP geometric mean antibody titre (GMT) was 2.0 microg/ml. The seroprotection rates for diphtheria and tetanus (> or = 0.01 IU/ml), poliovirus types 1, 2 and 3 (> or = 8 1/dil U) and hepatitis B were all 100%. Anti-polio GMTs were very high, 1 453, 1 699 and 2 398 (1/dil U) for types 1, 2 and 3, respectively. The seroconversion/vaccine response rates to pertussis antigens (4-fold increase in antibody concentration) were 97.5% for PT and 83.9% for FHA. CONCLUSIONS: The DTaP-IPV//PRP T vaccine was highly immunogenic at 6, 10 and 14 weeks of age in infants in South Africa, was compatible with the monovalent hepatitis B vaccine, and was well tolerated.

One-year post-primary antibody persistence and booster immune response to a DTaP-IPV//PRP~T vaccine (Pentaxim) given at 18 - 19 months of age in South African children primed at 6, 10 and 14 weeks of age with the same vaccine.

OBJECTIVE: To assess the immunogenicity and safety of a pentavalent diphtheria, tetanus, acellular pertussis, inactivated poliovirus, Hib polysaccharide-conjugate vaccine booster. DESIGN, SETTING AND PARTICIPANTS: A DTaP-IPV//PRP~T vaccine (Pentaxim, a Sanofi Pasteur AcXim family vaccine) was given to 182 healthy children in South Africa at 18 - 19 months of age following priming with the same vaccine plus a monovalent hepatitis B vaccine at 6, 10 and 14 weeks of age. Outcome measures. Seroprotection (SP) and seroconversion (SC) rates, geometric mean titres (GMTs) and concentrations (GMCs) were assessed before, and 1 month after, the booster dose. Safety was assessed using parental reports. RESULTS: One month after primary vaccination, at least 94.3% of participants were seroprotected against tetanus (≥ 0.01 IU/ml), diphtheria (≥ 0.01 IU/ml), poliovirus (≥ 8 1/dil) and Haemophilus influenzae type b (Hib) infection (≥ 0.15 µg/ml). Before the booster dose, the SP rates ranged from 65.7% to 100%. One month after the booster dose, SP rates were 97.7% for Hib (anti-PRP titre 1.0 µg/ml), 100.0% for diphtheria (≥ 0.1 IU/ml) and 100% for tetanus (≥ 0.1 IU/ml) and poliovirus types 1, 2, 3 (≥ 8 1/dil). At least 95.7% of participants had 4 fold post-booster increases in anti-pertussis antibody titres. GMTs increased from 11.21 to 465.51 EU/ml and from 12.89 to 520.35 EU/ml for anti-PT and anti-FHA respectively. Anti-PRP GMT increased from 0.35 to 47.01 µg/ml. The DTaP-IPV//PRP~T vaccine booster was well tolerated, with fever ≥ 39.0°C in only 1.7% of participants. CONCLUSIONS: Antibody persistence following priming was satisfactory. The pentavalent DTaP-IPV//PRP~T vaccine booster was highly immunogenic and well tolerated.

Safety, Reactogenicity, and Immunogenicity of Human Rotavirus Vaccine RIX4414 in Human Immunodeficiency Virus-positive Infants in South Africa.

BACKGROUND: rotavirus and human immunodeficiency virus (HIV) infections are a cause of great public health concern in developing countries. The current study evaluated the safety, reactogenicity, and immunogenicity of RIX4414 vaccine in asymptomatic or mildly symptomatic (clinical stages I and II according to WHO classification) HIV-infected South African infants. METHODS: a total of 100 HIV-positive infants aged 6 to 10 weeks enrolled in this double-blind, 1:1 randomized, placebo-controlled study were allocated into 2 groups to receive 3 doses of RIX4414 vaccine/placebo according to a 0-, 1-, and 2-month schedule. Routine vaccines were concomitantly administered. Solicited and unsolicited symptoms were recorded for 15 and 31 days after each dose, respectively. Serious adverse events were recorded throughout the study period. Serum antirotavirus IgA concentrations (enzyme-linked immunosorbent assay, cut-off ≥ 20 U/mL) and the immunodeficiency status were determined at screening and 2 months post-Dose 3. Stool samples were analyzed for rotavirus using enzyme-linked immunosorbent assay at predetermined points and during diarrhea episodes. RESULTS: all symptoms (solicited and unsolicited) occurred at a similar frequency in both groups. Six fatal serious adverse events in RIX4414 and 9 in placebo groups were reported. At 2 months post-Dose 3, the seroconversion rates were 57.1% (95% CI: 34-78.2) in RIX4414 and 18.2% (95% CI: 5.2-40.3) in the placebo group. The mean absolute CD4 cell count, CD4 percentage, and HIV-1 viral load were comparable in both groups at screening and 2 months post-Dose 3. Rotavirus shedding peaked at Day 7 after Dose 1 of RIX4414 with prolonged shedding was observed in 1 infant only. CONCLUSIONS: : Three doses of RIX4414 vaccine was tolerated well by the South African HIV-positive infants. A satisfactory immune response was mounted without aggravating their immunologic or HIV condition.