Practical Management of HIV-Associated Anemia in Resource-Limited Settings: Prospective Observational Evaluation of a New Mozambican Guideline.

Mozambique's updated guideline for management of HIV-associated anemia prompts clinicians to consider opportunistic conditions, adverse drug reactions, and untreated immunosuppression in addition to iron deficiency, intestinal helminthes, and malaria. We prospectively evaluated this guideline in rural Zambézia Province. Likely cause(s) of anemia were determined through prespecified history, physical examination, and laboratory testing. Diagnoses were "etiologic" if laboratory confirmed (sputum microscopy, blood culture, Plasmodium falciparum malaria rapid test) or "syndromic" if not. To assess hemoglobin response, we used serial point-of-care measurements. We studied 324 ambulatory, anemic (hemoglobin <10 g/dl) HIV-infected adults. Study clinicians treated nearly all [315 (97.2%)] for suspected iron deficiency and/or helminthes; 56 (17.3%) had laboratory-confirmed malaria. Other assigned diagnoses included tuberculosis [30 (9.3%)], adverse drug reactions [26 (8.0%)], and bacteremia [13 (4.1%)]. Etiologic diagnosis was achieved in 79 (24.4%). Of 169 (52.2%) subjects who improved (hemoglobin increase of ≥1 g/dl without indications for hospitalization), only 65 (38.5%) received conventional management (iron supplementation, deworming, and/or antimalarials) alone. Thirty (9.3%) died and/or were hospitalized, and 125 (38.6%) were lost to follow-up. Multivariable linear and logistic regression models described better hemoglobin responses and/or outcomes in subjects with higher CD4(+) T-lymphocyte counts, pre-enrollment antiretroviral therapy and/or co-trimoxazole prophylaxis, discontinuation of zidovudine for suspected adverse reaction, and smear-positive tuberculosis. Adverse outcomes were associated with fever, low body mass index, bacteremia, esophageal candidiasis, and low or missing CD4(+) T cell counts. In this severely resource-limited setting, successful anemia management often required interventions other than conventional presumptive treatment, thus supporting Mozambique's guideline revision.

Identification of Invasive Salmonella Enterica Serovar Typhimurium ST313 in Ambulatory HIV-Infected Adults in Mozambique.

INTRODUCTION: Despite evidence describing the burden of invasive non-typhoidal salmonella (iNTS) disease in sub-Saharan Africa, iNTS is not recognized as a priority within global health policy institutions. Recently, Salmonella enterica serovar Typhimurium, sequence type (ST) 313, has been identified as the predominant cause of iNTS disease in multiple sub-Saharan African countries. MATERIALS AND METHODS: We conducted multilocus sequence typing (MLST) to determine the prevalence of the ST313 genotype in a sample of blood isolates from ambulatory HIV-infected Mozambican adults with iNTS disease. RESULTS: Of the 29 samples of NTS obtained and analyzed by MLST, all (29/29) were assigned the ST313 sequence type based on the set of allele types derived from each of the seven loci. For quality control, five randomly selected strains taken from the original cultures were confirmed as ST313, and the positive control strain SL3261 (taken from the original culture) was categorized as S. Typhimurium ST19. CONCLUSION: S. Typhimurium ST313 is an important example of a widely distributed pathogen that lacks a coordinated strategy for control. The highly vulnerable populations at risk for ST313 infection in Mozambique, and within the region, would benefit greatly from the development of new policy and on-the-ground capacity to support increased surveillance, prevention, and treatment initiatives.

Management of fever in ambulatory HIV-infected adults in resource-limited settings: prospective observational evaluation of a new Mozambican guideline.

A new Mozambican guideline for management of fever in HIV-infected adults requires malaria testing and systematic consideration of specific alternative diagnoses (eg, tuberculosis and bacterial infections) in addition to malaria. We conducted a prospective observational study of the guideline's performance. Of 258 HIV-infected subjects with axillary temperature ≥37.5° C or history of fever, 76.0% improved, 13.6% died or were hospitalized, and 10.5% were lost to follow-up. In multivariate analyses, factors associated with adverse outcomes were bacterial blood stream infection, syndromically diagnosed tuberculosis, lower CD4 T-lymphocyte count, no antiretroviral therapy, lower body mass index, lower hemoglobin, and nonprescription of antibiotics.

Bacteremia as a cause of fever in ambulatory, HIV-infected Mozambican adults: results and policy implications from a prospective observational study.

Fever is typically treated empirically in rural Mozambique. We examined the distribution and antimicrobial susceptibility patterns of bacterial pathogens isolated from blood-culture specimens, and clinical characteristics of ambulatory HIV-infected febrile patients with and without bacteremia. This analysis was nested within a larger prospective observational study to evaluate the performance of new Mozambican guidelines for fever and anemia in HIV-infected adults (clinical trial registration NCT01681914, www.clinicaltrials.gov); the guidelines were designed to be used by non-physician clinicians who attended ambulatory HIV-infected patients in very resource-constrained peripheral health units. In 2012 (April-September), we recruited 258 HIV-infected adults with documented fever or history of recent fever in three sites within Zambézia Province, Mozambique. Although febrile patients were routinely tested for malaria, blood culture capacity was unavailable in Zambézia prior to study initiation. We confirmed bacteremia in 39 (15.1%) of 258 patients. The predominant organisms were non-typhoid Salmonella, nearly all resistant to multiple first-line antibiotics (ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole). Features most associated with bacteremia included higher temperature, lower CD4+ T-lymphocyte count, lower hemoglobin, and headache. Introduction of blood cultures allowed us to: 1) confirm bacteremia in a substantial proportion of patients; 2) tailor specific antimicrobial therapy for confirmed bacteremia based on known susceptibilities; 3) make informed choices of presumptive antibiotics for patients with suspected bacteremia; and 4) construct a preliminary clinical profile to help clinicians determine who would most likely benefit from presumptive bacteremia treatment. Our findings demonstrate that in resource-limited settings, there is urgent need to expand local microbiologic capacity to better identify and treat cases of bacteremia in HIV-infected and other patients, and to support surveillance. Data on the prevalence and susceptibility patterns of important pathogens can guide national formulary and prescribing practices.