The American Journal of Tropical Medicine and Hygiene - Online First

The main objective of this study was to assess whether training of private health providers and community sensitization on the importance of effective prompt care seeking and the need for referral could improve treatment of sick children in the private health sector in Uganda. Private providers were trained to diagnose and treat sick children according to the integrated community case management (iCCM) guidelines. In the control arm, routine services were offered. The outcomes were seeking care within 24 hours of onset of symptoms and appropriate case management for malaria, pneumonia, and diarrhea among children aged < 5 years. A total of 10,809 sick children (5,955 in the intervention arm and 4,854 in the control arm) presented for diagnosis and treatment. The percentage seeking care within 24 hours of onset of symptoms was 45.4% (95% CI 36.0–48.8) in the intervention arm versus 43.9% (95% CI 38.1–49.8) in the control arm (P = 0.04). Adherence to malaria rapid diagnostic test (mRDT) results was high, with 1,459 (94.3%) in the intervention arm versus 1,402 (83.0%) in the control arm (P = 0.04). Appropriate treatment of mRDT-positive children with artemisinin-based combination therapy was seen in 93.1% (95% CI 88.5–97.7) in the intervention arm versus 85.1% (95% CI 78.6–91.7) in the control arm (P = 0.03). Adherence to iCCM guidelines was very high: 89.1% of children with diarrhea in the intervention arm and 80.4% in the control arm were given oral rehydration salts and zinc (P = 0.01). Of the children with a respiratory rate > 40 breaths/minute, 1,596 (85.1%) in the intervention arm versus 104 (54.5%) in the control arm were given amoxicillin (P = 0.01). In conclusion, the intervention improved treatment of malaria, pneumonia, and diarrhea because of provider adherence to treatment guidelines. The policy implications of these findings are to initiate a dialogue at district and national levels on how to scale up the intervention in the private sector. NCT02450630 registered with ClinicalTrials.gov: May 9, 2015.

Point-of-care urine-lipoarabinomannan (LAM) Alere Determine TB-LAM assay has shown utility diagnosing tuberculosis (TB) in HIV-positive, severely immunocompromised, TB-symptomatic patients. We assessed LAM results in severely immunocompromised patients, who had LAM systematically performed at new or follow-up HIV consultations. This was a prospective, observational study on consecutive ambulatory, > 15-year-old HIV-positive patients with CD4 < 100 cells/µL in Mozambique. Clinical assessments and LAM were performed for all and microscopy, Xpert, sputum culture, and chest X-ray for LAM-positive participants. Patients were followed up for 6 months. Of 360 patients, half were ART-naive. Lipoarabinomannan positivity was 11.9% (43/360), higher among symptomatic patients compared with asymptomatic: 18.5% (30/162), and 6.6% (13/198), respectively, P = 0.001. Tuberculosis was bacteriologically confirmed in 6/35 LAM-positive patients (2 of them asymptomatic). Lipoarabinomannan positivity was associated with higher risk of mortality (aOR:4.48, 95% CI: 1.24–16.23, P = 0.022). Systematic urine-LAM allows for rapid TB treatment initiation in severely immunocompromised HIV ambulatory patients and identifies patients at a higher risk of death.

We describe hypoxemic pneumonia prevalence in outpatient and inpatient settings, in-hospital mortality, and clinical guideline performance for identifying hypoxemia in young infants in Malawi. In this retrospective analysis of a prospective cohort study, we investigate infants younger than 2 months participating in pneumonia surveillance at seven hospitals and 18 outpatient health centers in Malawi between 2011 and 2014. Logistic regression, multiple imputations with chained equations, and pattern mixture modeling were used to determine the association between peripheral oxyhemoglobin saturation (SpO2) levels and hospital mortality. We describe referral recommendations based on clinical characteristics and SpO2 distributions. Among 1,879 analyzed cases, SpO2 < 90% was more prevalent among outpatient health center cases than that among hospitalized cases (22.6% versus 13.5%, 95% CI: 17.6–28.4% and 12.0–15.3%, respectively). A larger proportion of hospitalized infants had signs of respiratory distress than infants at health centers (67.7% versus 56.6%, P < 0.001) and the signs were higher in male versus female infants (56.7% versus 40.6%, P < 0.001). An SpO2 of 90–92% and < 90% was associated with similarly increased odds of in-hospital mortality (adjusted odds ratio [aOR]: 4.3 and 4.4, 95% CI: 1.7–11.1 and 1.8–10.5, respectively). Unrecorded, or unobtainable, SpO2 was highly associated with mortality (n = 127, aOR: 18.1; 95% CI: 7.6–42.8). Four of 22 (18%) infants at health centers who did not meet clinical referral criteria had an SpO2 ≤ 92%. Clinicians should consider hospital referral in young infants with SpO2 ≤ 92%. Infants with unobtainable SpO2 readings should be considered a high-risk group, and hospital referral of these cases may be appropriate.

A cluster, randomized control trial was conducted to assess the effects of social marketing approach on purchase rates and water treatment behavior of Klorfasil, a chlorine-based household water treatment product among seven villages in Thomassique, Haiti, from May to December 2016. Villages were randomized to the free-trial (257 households) or cost-sharing (240 households) group. Households in the free-trial group were allowed 30 days of free Klorfasil use before purchase decision. Households who purchased Klorfasil were then followed up for 30, 60, and 180 days. At the last follow-up, respondents were asked if they would like to repurchase Klorfasil. Questionnaire survey and water quality assessment by residual-free chlorine were conducted in each survey. Chi-square test, t-test, and logistic regression were applied. The first purchase rate of the cost-sharing group was significantly higher than that of the free-trial group (79.2% versus 67.3%). By contrast, the repurchase rate of the free-trial group was higher (82.9% versus 66.3%). However, the overall repurchase rate was 71.6% and the proportion of long-term users was significantly higher in the cost-sharing group (56% versus 47%). Water treatment rates in the cost-sharing group were significantly higher than those in the free-trial group in the first and final surveys (odds ratio [OR] = 0.15, OR = 0.32). Households with high and medium economic status both had significantly higher purchase rates than low economic status households (OR = 4.40, OR = 1.94). Households with higher educated respondents had significantly better water treatment practices (OR = 2.15). The free-trial approach did not increase the first purchase rate but increased the repurchase rate later. The cost-sharing approach significantly encouraged long-term usage.

In posterior reversible encephalopathy syndrome, brain magnetic resonance imaging (MRI) reveals bilateral occipital, parietal, and subcortical white matter hyperintensities on T2/fluid-attenuated inversion recovery (FLAIR) sequences. After treatment, imaging abnormalities are usually reversible. Eclampsia is the most frequent cause of posterior reversible encephalopathy syndrome in pregnancy. We report a 24-year-old woman, who presented to our clinic 4 weeks after normal vaginal delivery with bilateral vision loss. Loss of vision was first noticed in the 20th week of pregnancy. Even after delivery, her vision did not improve. In the postpartum period, she started having periodic myoclonic jerks. Electroencephalography demonstrated periodic generalized discharges. A brain MRI performed in the 20th week of the antepartum period showed bilateral parieto-occipital cortical white matter T2/FLAIR hyperintensities. A follow-up brain MRI, 5 months later, revealed marked reversal of white matter signal changes. Cerebrospinal fluid examination revealed raised anti-measles antibody titer, confirming the diagnosis of subacute sclerosing panencephalitis. In conclusion, in a patient with SSPE during the postpartum period, cortical vision loss and parieto-occipital white matter T2/FLAIR hyperintensities can simulate eclampsia. Inadvertent treatment with magnesium sulfate is likely if the diagnosis is missed.

During the 2016 Zika pandemic in Brazil, women’s perceptions of infection risk, ability to adhere to Zika prevention strategies, or access to services following exposure were not emphasized in the public health response. Women in Fortaleza, Brazil, responded to a questionnaire on social factors related to perceived Zika risk and access to health care in June 2016. Data were coded using prespecified categories, and response frequency was reported. Of 37 respondents, most reported a lack of public services to support mosquito control (n = 19) or delayed access to reproductive health care (n = 14). Only 22% described specific maternal risks or fetal outcomes as a consequence of Zika infection. Respondents indicated an overall disconnect between public health efforts and women’s perceptions of their reproductive control, including limited support concerning microcephaly in infants. Interventions targeting Zika may require a greater emphasis on strengthening health systems and infrastructure to realistically prevent transmission.

Resistance to anti-leprosy drugs is on the rise. Several studies have documented resistance to rifampicin, dapsone, and ofloxacin in patients with leprosy. We looked for point mutations within the folP1, rpoB, and gyrA gene regions of the Mycobacterium leprae genome predominantly in the neural form of leprosy. DNA samples from 77 nerve tissue samples were polymerase chain reaction (PCR)-amplified for M leprae DNA and sequenced for drug resistance–determining regions of genes rpoB, folP1, and gyrA. The mean age at presentation and onset was 38.2 ± 13.4 (range 14–71) years and 34.9 ± 12.6 years (range 10–63) years, respectively. The majority had borderline tuberculoid leprosy (53 [68.8%]). Mutations associated with resistance were identified in 6/77 (7.8%) specimens. Mutations seen were those associated with resistance to rifampicin, ofloxacin, and dapsone. All the six patients were drug-naive. The clinical and pathological manifestations in this group did not differ from the drug-sensitive group. This study highlights the occurrence of resistance to the standard multidrug therapy and ofloxacin in leprosy. Among the entire cohort, 1/77 (1.3%) showed resistance to rifampicin, 2/77 (2.6%) to dapsone, and 5/77 (6.4%) to ofloxacin. Six new patients showing infection by mutant strains indicated the emergence of primary resistance. Resistance to ofloxacin could be due to frequent use of quinolones for many bacterial infections. The results of the study indicate the need for development of a robust and strict surveillance system for detecting drug resistance in leprosy in India.

Anemia is an increasingly recognized problem in sub-Saharan Africa. To determine the magnitude, severity, and associated factors of anemia among hospitalized children aged 6–59 months, HIV-infected and HIV-exposed uninfected children (a child born to a known HIV-infected mother) with a documented fever or history of fever within the prior 24 hours of hospital admission (N = 413) were included in this analysis. Of 413 children enrolled, 364 (88%) were anemic, with 53% classified as mild anemia (hemoglobin [Hb] 7–9.9 g/dL). The most common diagnoses associated with hospital admission included acute respiratory illness (51%), malnutrition (47%), gastroenteritis/diarrhea (25%), malaria (17%), and bacteremia (13%). A diagnosis of malaria was associated with a decrease in Hb by 1.54 g/dL (P < 0.001). In HIV-infected patients, malaria was associated with a similar decrease in Hb (1.47 g/dL), whereas a dual diagnosis of bacteremia and malaria was associated with a decrease in Hb of 4.12 g/dL (P < 0.001). No difference was seen in Hb for patients on antiretroviral therapy versus those who were not. A diagnosis of bacteremia had a roughly 4-fold increased relative odds of death during hospitalization (adjusted odds ratio = 3.97; 95% CI: 1.61, 9.78; P = 0.003). The etiology of anemia in high-burden malaria, HIV, tuberculosis, and poor nutrition countries is multifactorial, and multiple etiologies may be contributing to one’s anemia at any given time. Algorithms used by physician and nonphysician clinicians in Mozambique should incorporate integrated and non–disease specific approaches to pediatric anemia management and should include improved access to blood culture.

Helicobacter pylori (H. pylori), a gram-negative pathogen, has been shown to colonize multiple organs and cause various forms of extra-gastrointestinal diseases. The association of H. pylori infection with vitamin D status in apparently healthy children remained unclear; therefore, we investigated the relationship between vitamin D and H. pylori infection among apparently healthy infants and toddlers. In this large cross-sectional study, the examination data of children were collected from January 2013 to September 2017 in the Center for Children’s Health Care. Among these children, 6,896 infants and toddlers were screened for our study. Helicobacter pylori infection and vitamin D status were the main indicators, and micronutrients (zinc, iron, copper, magnesium), and growth parameters (height, weight, and weight for age Z score [WAZ], height for age Z score [HAZ]) were also analyzed in this study. Among the 6,896 infants and toddlers, the detection rate of H. pylori seropositivity was 30.6%. The prevalence of vitamin D deficiency in H. pylori seropositive and seronegative groups was 20.7% and 12.1%, respectively (P < 0.001). The logistic regression analysis suggested children with H. pylori–positive antibody were 2.06 times more likely to be vitamin D deficient compared with children who had negative H. pylori antibody (odds ratio: 2.06; 95% CI: 1.77, 2.38) after controlling for confounding factors. These data suggested that there was a significant association between H. pylori seropositivity and vitamin D deficiency in children aged 6–36 months, which would make a contribution to the treatment and monitoring of vitamin D deficiency and H. pylori infection.