The adequacy of the World Health Organization’s Integrated Management of Childhood Illness (IMCI) antimicrobial guidelines for the treatment of suspected severe bacterial infections is dependent on a low prevalence of antimicrobial resistance (AMR). We describe trends in etiologies and susceptibility patterns of bloodstream infections (BSI) in hospitalized children in Malawi. We determined the change in the population-based incidence of BSI in children admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi (1998–2017). AMR profiles were assessed by the disc diffusion method, and trends over time were evaluated. A total 89643 pediatric blood cultures were performed, and 10621 pathogens were included in the analysis. Estimated minimum incidence rates of BSI for those ≤5 years of age fell from a peak of 11.4 per 1000 persons in 2002 to 3.4 per 1000 persons in 2017. Over 2 decades, the resistance of Gram-negative pathogens to all empiric, first-line antimicrobials (ampicillin/penicillin, gentamicin, ceftriaxone) among children ≤5 years increased from 3.4% to 30.2% (P < .001). Among those ≤60 days, AMR to all first-line antimicrobials increased from 7.0% to 67.7% (P < .001). Among children ≤5 years, Klebsiella spp. resistance to all first-line antimicrobial regimens increased from 5.9% to 93.7% (P < .001). The incidence of BSI among hospitalized children has decreased substantially over the last 20 years, although gains have been offset by increases in Gram-negative pathogens’ resistance to all empiric first-line antimicrobials. There is an urgent need to address the broader challenge of adapting IMCI guidelines to the local setting in the face of rapidly-expanding AMR in childhood BSI.

Acute febrile illness is a common cause of hospital admission, and its associated infectious causes contribute to substantial morbidity and death among children worldwide, especially in low- and middle-income countries. Declining transmission of malaria in many regions, combined with the increasing use of rapid diagnostic tests for malaria, has led to the increasing recognition of leptospirosis, rickettsioses, respiratory viruses, and arboviruses as etiologic agents of fevers. However, clinical discrimination between these etiologies can be difficult. Overtreatment with antimalarial drugs is common, even in the setting of a negative test result, as is overtreatment with empiric antibacterial drugs. Viral etiologies remain underrecognized and poorly investigated. More-sensitive diagnostics have led to additional dilemmas in discriminating whether a positive test result reflects a causative pathogen. Here, we review and summarize the current epidemiology and focus particularly on children and the challenges for future research.

Background and Objective: Current guidelines strongly recommend collection of blood cultures (BCs) in children requiring hospitalization for presumed moderate to severe bacterial community-acquired pneumonia (CAP). Our objective was to systematically review the international pediatric literature to evaluate how often BCs are positive in hospitalized children with CAP, identify the most commonly isolated pathogens, and determine the impact of positive BCs on clinical management. Methods: We identified articles in PubMed and Scopus published from January 1970 through December 2013 that addressed BCs in children with CAP. We extracted total number of BCs collected and prevalence of positive BCs and used meta-regression to evaluate whether subgroups had any impact on prevalence. Results: Meta-analysis showed that the overall prevalence of positive BCs was 5.14% (95% confidence interval 3.61–7.28). Studies focusing on severe CAP had a significant effect on prevalence (P = .008), at 9.89% (95% CI 6.79–14.19) compared with 4.17% (95% confidence interval 2.79–6.18) for studies not focusing on severe CAP. The most commonly isolated organisms were Streptococcus pneumoniae (76.7%) followed by Haemophilus influenzae (3.1%) and Staphylococcus aureus (2.1%). Contaminants accounted for 14.7%. Only 3 studies reported on BC-driven change in management, with contrasting findings. Conclusions: BCs in pediatric CAP identified organisms in only a small percentage of patients, predominantly S. pneumoniae. False-positive BC rates can be substantial. The 3 studies that examined BC-driven changes in management had conflicting results. This systematic review was limited by heterogeneous case definitions, which may overestimate the true prevalence of positive BCs in hospitalized children.

Background: We evaluated the efficacy, pharmacokinetics (PK), and safety of clofazimine (CFZ) in patients living with human immunodeficiency virus (HIV) with cryptosporidiosis. Methods: We performed a randomized, double-blind, placebo-controlled study. Primary outcomes in part A were reduction in Cryptosporidium shedding, safety, and PK. Primary analysis was according to protocol (ATP). Part B of the study compared CFZ PK in matched individuals living with HIV without cryptosporidiosis. Results: Twenty part A and 10 part B participants completed the study ATP. Almost all part A participants had high viral loads and low CD4 counts, consistent with failure of antiretroviral (ARV) therapy. At study entry, the part A CFZ group had higher Cryptosporidium shedding, total stool weight, and more diarrheal episodes compared with the placebo group. Over the inpatient period, compared with those who received placebo, the CFZ group Cryptosporidium shedding increased by 2.17 log2 Cryptosporidium per gram stool (95% upper confidence limit, 3.82), total stool weight decreased by 45.3 g (P = .37), and number of diarrheal episodes increased by 2.32 (P = .87). The most frequent solicited adverse effects were diarrhea, abdominal pain, and malaise. One placebo and 3 CFZ participants died during the study. Plasma levels of CFZ in participants with cryptosporidiosis were 2-fold lower than in part B controls. Conclusions: Our findings do not support the efficacy of CFZ for the treatment of cryptosporidiosis in a severely immunocompromised HIV population. However, this trial demonstrates a pathway to assess the therapeutic potential of drugs for cryptosporidiosis treatment. Screening persons living with HIV for diarrhea, and especially Cryptosporidium infection, may identify those failing ARV therapy. Clinical Trials Registration: NCT03341767.

Malawi declared a state of national disaster due to the COVID-19 pandemic on 20th March 2020 and registered its first confirmed coronavirus case on the 2 April 2020. The aim of this paper was to document policy decisions made in response to the COVID-19 pandemic from January to August 2020. We reviewed policy documents from the Public Health Institute of Malawi, the Malawi Gazette, the Malawi Ministry of Health and Population and the University of Oxford Coronavirus Government Response Tracker. We found that the Malawi response to the COVID-19 pandemic was multisectoral and implemented through 15 focused working groups termed clusters. Each cluster was charged with providing policy direction in their own area of focus. All clusters then fed into one central committee for major decisions and reporting to head of state. Key policies identified during the review include international travel ban, school closures at all levels, cancellation of public events, decongesting workplaces and public transport, and mandatory face coverings and a testing policy covering symptomatic people. Supportive interventions included risk communication and community engagement in multiple languages and over a variety of mediums, efforts to improve access to water, sanitation, nutrition and unconditional social-cash transfers for poor urban and rural households.