Association of Stress, Glucocorticoid Receptor, and FK506 Binding Protein Gene Polymorphisms With Internalizing Disorders Among HIV-Infected Children and Adolescents From Kampala and Masaka Districts-Uganda.

Children and adolescents living with human immunodeficiency virus (CA-HIV) suffer a considerable burden of internalizing disorders (IDs; depressive and anxiety disorders). Environmental and genetic factors have been reported to influence the vulnerability to IDs in western settings; however, their role among African populations remains inadequately explored. We investigated the individual and interactive effects of stress and single-nucleotide polymorphisms within the FK506 binding protein 5 (rs1360780) and glucocorticoid receptor (rs10482605) genes on ID status in a cohort of CA-HIV in Uganda. We genotyped rs10482605 (309 cases and 315 controls) and rs1360780 (350 cases and 335 controls) among CA-HIV with and without IDs using Kompetitive Allele-Specific PCR. Socio-demographic variables, as well as allele and genotype distributions, were compared between cases and controls using chi-square tests. Genotypes were assessed for Hardy-Weinberg equilibrium. Composite indices of recent and chronic stress classes were also generated. A hierarchical cluster analysis was used to generate cutoff points within each of the indices of recent and chronic stress. Logistic regression was used to assess the association between IDs and each of recent stress, chronic stress, and the investigated genotypes. The interaction effect of chronic/recent stress on the association between each of the polymorphisms and IDs was determined using a likelihood ratio test. We observed no significant association between IDs and rs1360780 and rs10482605 polymorphisms within the FKBP5 and glucocorticoid receptor genes, respectively (P > 0.050). Severe recent stress increased the vulnerability to IDs among CA-HIV (P = 0.001). We did not observe any gene-environment effect on vulnerability to IDs in this population. These findings support the currently held opinion that polymorphisms at single genetic loci only contribute a very small effect to the genetic vulnerability to IDs.

Differential pre-pandemic breast milk IgA reactivity against SARS-CoV-2 and circulating human coronaviruses in Ugandan and American mothers.

OBJECTIVE: Uganda has registered fewer coronavirus disease 2019 (COVID-19) cases and deaths per capita than Western countries. The lower numbers of cases and deaths might be due to pre-existing cross-immunity induced by circulating common cold human coronaviruses (HCoVs) before the COVID-19 pandemic. To investigate pre-existing mucosal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, a comparison was performed of IgA reactivity to SARS-CoV-2 and HCoVs in milk from mothers collected in 2018. METHODS: Ugandan and United States milk samples were run on an ELISA to measure specific IgA to SARS-CoV-2 and HCoVs NL63, OC43, HKU1, and 229E spike proteins. Pooled plasma from United States SARS-CoV-2-positive and negative cases were positive and negative controls, respectively. RESULTS: One Ugandan mother had high milk IgA reactivity against all HCoVs and SARS-CoV-2 spike proteins. Ugandan mothers had significantly higher IgA reactivity against the betacoronavirus HCoV-OC43 than United States mothers (P = 0.018). By contrast, United States mothers had significantly higher IgA reactivity against the alphacoronaviruses HCoV-229E and HCoV-NL63 than Ugandan mothers (P < 0.0001 and P = 0.035, respectively). CONCLUSION: Some Ugandan mothers have pre-existing HCoV-induced IgA antibodies against SARS-CoV-2, which may be passed to infants via breastfeeding.

Mice Pups Breastfed by Foster Mothers Whose Breast Milk Contains Plasmodium falciparum Recombinant SE36 Antigen Develop Specific Antibodies.

Intranasal instillation of SE36, a malaria vaccine candidate antigen, in lactating BALB/c strain (derived from the Bagg and albino laboratory inbred mice) female mice resulted in the appearance of the antigen in breast milk as demonstrated by sandwich ELISA and Western blot. Pups born of immunologically naive mice and breastfed on lactating foster mothers exposed intranasally to SE36 developed IgG anti-SE36 antibodies. These data demonstrate that maternal immunization in mice by this route in lactating mothers can result in active immunization of offspring via ingestion of breast milk containing antigen. If confirmed in a nonhuman primate model and in human subjects, this strategy might be transformative for vaccination against malaria and other infant killer infectious diseases.

Using the Ultrasensitive Alere Plasmodium falciparum Malaria Ag HRP-2™ Rapid Diagnostic Test in the Field and Clinic in Northeastern Uganda.

The ultrasensitive Alere Plasmodium falciparum Malaria Ag histidine-rich protein 2 rapid diagnostic test (Alere uRDT, Suwon City, South Korea) is a new diagnostic tool which is more expensive than other malaria rapid diagnostic tests (RDTs) routinely used in Ugandan clinics. The manufacturer recommends testing samples within 2 days and scoring results after 20 minutes, which may be impractical in high-volume resource-poor clinics. We compared testing by the Alere Ag rapid diagnostic test (uRDT), CareStart RDT, microscopy, and an ultrasensitive I8S rRNA quantitative reverse transcription polymerase chain reaction (qRT-PCR) using survey and clinical samples. For the Alere uRDT, we used survey blood samples stored at 4°C for 44 days and for some clinical samples deliberately scored results beyond 20 minutes. The Alere uRDT and qRT-PCR identified asymptomatic parasitemia cases in 56% and 72%, respectively, of survey samples originally scored as negative by the CareStart RDT. Using qRT-PCR as a gold standard, the Alere uRDT was superior to the CareStart RDT in estimating asymptomatic parasite prevalence in a cross-sectional survey (P = 0.007) and in detection of clinically significant malaria; both RDTs were comparable in detecting asymptomatic parasitemia in the clinic (P = 0.599). Scoring Alere uRDT results at 20 minutes produced valid results confirmed by the CareStart RDT, but there was a consistent background; scoring the Alere uRDT beyond 20 minutes produced false-positive results. The Alere uRDT outperformed the CareStart RDT (ACCESSBIO, Somerset, NJ) in a field survey in estimating malaria prevalence and in the clinic for symptomatic malarial illness. It produced reliable results using samples stored at 4°C for 44 days, but test results read beyond 20 minutes were invalid.

Molecular Characterization of Salmonella from Human and Animal Origins in Uganda.

Sporadic Salmonella outbreaks with varying clinical presentations have been on the rise in various parts of Uganda. The sources of outbreaks and factors underlying the different clinical manifestation are curtailed by paucity of information on Salmonella genotypes and the associated virulence genes. This study reports molecular diversity of Salmonella enterica and their genetic virulence profiles among human and animal isolates. Characterization was done using Kauffman-White classification scheme and virulence genes analysis using multiplex PCR. Overall, 52% of the isolates belonged to serogroup D, 16% to serogroup E, 15% to poly F, H-S, and 12% to serogroup B. Serogroups A, C1, and C2 each consisted of only one isolate representing 5%. Virulence genes located on SPI-1 [spaN and sipB] and on SPI-2 [spiA] in addition to pagC and msgA were equally distributed in isolates obtained from all sources. Plasmid encoded virulence gene spvB was found in <5% of isolates from both human epidemic and animal origins whereas it occurred in 80% of clinical isolates. This study reveals that serogroup D is the predominant Salmonella serogroup in circulation and it is widely shared among animals and humans and calls for joint and coordinated surveillance for one health implementation in Uganda.