Soil-transmitted helminths: A critical review of the impact of co-infections and implications for control and elimination.

Researchers have raised the possibility that soil-transmitted helminth (STH) infections might modify the host's immune response against other systemic infections. STH infections can alter the immune response towards type 2 immunity that could then affect the likelihood and severity of other illnesses. However, the importance of co-infections is not completely understood, and the impact and direction of their effects vary considerably by infection. This review synthesizes evidence regarding the relevance of STH co-infections, the potential mechanisms that explain their effects, and how they might affect control and elimination efforts. According to the literature reviewed, there are both positive and negative effects associated with STH infections on other diseases such as malaria, human immunodeficiency virus (HIV), tuberculosis, gestational anemia, pediatric anemia, neglected tropical diseases (NTDs) like lymphatic filariasis, onchocerciasis, schistosomiasis, and trachoma, as well as Coronavirus Disease 2019 (COVID-19) and human papillomavirus (HPV). Studies typically describe how STHs can affect the immune system and promote increased susceptibility, survival, and persistence of the infection in the host by causing a TH2-dominated immune response. The co-infection of STH with other diseases has important implications for the development of treatment and control strategies. Eliminating parasites from a human host can be more challenging because the TH2-dominated immune response induced by STH infection can suppress the TH1 immune response required to control other infections, resulting in an increased pathogen load and more severe disease. Preventive chemotherapy and treatment are currently the most common approaches used for the control of STH infections, but these approaches alone may not be adequate to achieve elimination goals. Based on the conclusions drawn from this review, integrated approaches that combine drug administration with water, sanitation and hygiene (WASH) interventions, hygiene education, community engagement, and vaccines are most likely to succeed in interrupting the transmission of STH co-infections. Gaining a better understanding of the behavior and relevance of STH co-infections in the context of elimination efforts is an important intermediate step toward reducing the associated burden of disease.

Sibling Species Composition and Susceptibility Status of Anopheles gambiae s.l. to Insecticides Used for Indoor Residual Spraying in Eastern Uganda.

Background: Malaria remains one of the most critical disease causing morbidity and mortality in Uganda. Indoor residual spraying (IRS) and the use of insecticide-treated bed nets are currently the predominant malaria vector control interventions. However, the emergence and spread of insecticide resistance among malaria vectors threaten the continued effectiveness of these interventions to control the disease, particularly in high transmission areas. To inform decisions on vector control, the current study evaluated the Anopheles malaria vector species and their susceptibility levels to 0.1% bendiocarb and 0.25% pirimiphos-methyl insecticides used in IRS intervention program in Namutumba district, Eastern Uganda. Methods: Anopheles larvae were collected between March and May 2017 from different breeding sites in the parishes of Nsinze and Nawaikona in Nsinze sub-county and reared to adults to assess the susceptibility status of populations in the study area. Mosquitoes were identified using morphological keys and species-specific polymerase chain reaction (PCR) assays. Susceptibility tests were conducted on 2- to 5-day-old non-blood-fed adult female Anopheles that emerged using insecticide-impregnated papers with 0.1% bendiocarb and 0.25% pirimiphos-methyl following standard World Health Organization (WHO) insecticide susceptibility bioassays. A Log-probit regression model was used to derive the knock-down rates for 50% and 95% of exposed mosquitoes. Results: A total of 700 mosquito larvae were collected from different breeding sites. Morphological identification showed that 500 individuals that emerged belonged to Anopheles gambiae sensu lato (s.l.), the main malaria vector. The PCR results showed that the dominant sibling species under the A. gambiae complex was Anopheles arabiensis 99.5% (395/397). WHO bioassay tests revealed that the population of mosquitoes exhibited high levels of susceptibility (24-hour post-exposure mortality 98-100%) to both insecticides tested. The median knock-down time, KDT50, ranged from 6.6 to 81.4 minutes, while the KDT95 ranged from 21.6 to 118.9 minutes for 0.25% pirimiphos-methyl. The KDT50 for 0.1% bendiocarb ranged from 2.8 to 62.9 minutes, whereas the KDT95 ranged from 36.0 to 88.5 minutes. Conclusions: These findings indicate that bendiocarb and pirimiphos-methyl are still effective against the major malaria vector, A. arabiensis in Nsinze sub-county, Namutumba district, Uganda and can be effectively used for IRS. The study has provided baseline information on the insecticide susceptibility status on malaria vectors in the study area. However, routine continuous monitoring program of insecticide susceptibility and malaria vector composition is required so as to guide future decisions on insecticide use for IRS intervention toward malaria elimination and to track future changes in vector population.

Growth and Reproductive Performance of Edible Grasshopper (Ruspolia differens) on Different Artificial Diets.

Ruspolia differens (Serville) (Orthoptera: Tettigoniidae), also known as the 'edible grasshopper', 'African edible bush-cricket', and 'nsenene', is regarded as one of the most promising edible insect species that can be used for food, particularly in Sub-Saharan Africa. However, there is insufficient information on suitable diets and their effects on survival, adult weight, fecundity, and developmental time of this species, which are preconditions for large-scale production. In this study, we experimentally evaluated the effects of 12 diets (wheat bran, rice seed head, finger millet seed head, soya bran, maize bran, fresh maize comb, millet flour, chicken feed egg booster, simsim cake, sorghum seed head, powdered groundnut, and germinated finger millet), that are known to be accepted by R. differens, on their growth and reproductive parameters. The survival rate, developmental time, and adult weight varied considerably on the various diets. The highest nymphal survival rates, shortest development times, and highest adult weights were recorded for both sexes when fed fresh maize comb and germinated finger millet diet. Lifetime fecundity of females fed on germinated finger millet also was, on average, more than twice higher compared to other diets. The present study demonstrated that relatively inexpensive and locally available germinated finger millet, fresh maize seed (at the silking stage on the comb), sorghum seedhead, and finger millet seedhead could be successfully used to rear and sustain populations of R. differens. Our findings contribute to the future design of an effective mass-rearing system for this economically important edible insect.

Hookworm Infection among Pregnant Women at First Antenatal Visit in Lira, Uganda: A Cross-Sectional Study.

BACKGROUND: Hookworm infection in expectant mothers has adverse health effects on both the mothers and their unborn babies. Foetal effects are known to include intrauterine growth retardation and physical and mental growth retardation, while the mothers may develop anemia which could potentially result in death. Unfortunately, little is known about factors that may predispose a pregnant woman to infection by hookworm. In this study, we strived to determine not only the prevalence of hookworm infection among pregnant women attending their first antenatal visit during the current pregnancy in a local health center in northern Uganda but also factors that might predispose them to hookworm infection. METHOD: This cross-sectional study was conducted among 346 pregnant women from Ogur Health Center IV located in Lira district, northern Uganda. Stool samples were collected from each study participant and analyzed for hookworms. The independent variables listed in this study (participant's sociodemographic characteristics, preconception care, and sanitation factors) were obtained using a structured questionnaire. Data analysis, including calculation of adjusted ratios, was performed using STATA software (version 14). RESULTS: Prevalence of hookworm infection among pregnant women who attended their first antenatal visit at Ogur Health Center IV was 11% (n = 38). After controlling for confounders, factors found to be significantly associated with this infection among pregnant women here were gardening barefooted (adjusted odds ratio (AOR), 3.4; 95% confidence interval (CI), 1.6 to 7.5; P < 0.001) and fetching unsafe water shared with animals for domestic uses (AOR, 2.8; 95% CI, 1.3 to 6.2; P value of 0.002). CONCLUSION: Hookworm infection among pregnant women at Ogur Health Center IV in Lira district, at 11%, is a public health concern and significantly associated with barefoot gardening and fetching water from unsafe sources shared with animals. We, therefore, recommend that special emphasis during routine prenatal health education be placed on the use of protective footwear during farming and fetching water for domestic use from protected safe sources. Author Summary. Hookworm infection is a parasitic condition that more often goes unnoticed, yet it presents immense detrimental effects, especially to pregnant women and their unborn children. It is a chronic disease with accruing effects of blood depletion resulting in anemia. Anemia is, by far, one of the major causes of maternal morbidity and mortality in Uganda. Pregnant women are more prone to hookworm infection by virtue of their compromised immunity, secondary to the physiological process of pregnancy. We demonstrated here that hookworm infection still exists among pregnant women in Uganda. We also showed that gardening barefooted and fetching water for domestic uses from unsafe sources shared with animals were major factors associated with this helminthic infection. This study provides evidence necessary to influence decision making on prevention of hookworm infection in the study area.

Characterization of Evolutionarily Conserved Trypanosoma cruzi NatC and NatA-N-Terminal Acetyltransferase Complexes.

Protein N-terminal acetylation is a co- and posttranslational modification, conserved among eukaryotes. It determines the functional fate of many proteins including their stability, complex formation, and subcellular localization. N-terminal acetyltransferases (NATs) transfer an acetyl group to the N-termini of proteins, and the major NATs in yeast and humans are NatA, NatB, and NatC. In this study, we characterized the Trypanosoma cruzi (T. cruzi) NatC and NatA protein complexes, each consisting of one catalytic subunit and predicted auxiliary subunits. The proteins were found to be expressed in the three main life cycle stages of the parasite, formed stable complexes in vivo, and partially cosedimented with the ribosome in agreement with a cotranslational function. An in vitro acetylation assay clearly demonstrated that the acetylated substrates of the NatC catalytic subunit from T. cruzi were similar to those of yeast and human NatC, suggesting evolutionary conservation of function. An RNAi knockdown of the Trypanosoma brucei (T. brucei) NatC catalytic subunit indicated that reduced NatC-mediated N-terminal acetylation of target proteins reduces parasite growth.

High prevalence of Pfmdr-1 N86 and D1246 genotypes detected among febrile malaria outpatients attending Lira Regional Referral Hospital, Northern Uganda.

OBJECTIVE: To determine the prevalence of Plasmodium falciparum multi-drug resistant gene-1 (Pfmdr-1) N86Y and D1246Y genotypes among febrile malaria outpatients attending Lira Regional Referral Hospital, Uganda. RESULTS: Overall, 92.3% (n = 48/52) and 90% (n = 45/50) of the parasites detected carried the wild type alleles 1246D and N86, respectively. Only 7.7% (n = 4/52) and 10% (n = 5/50) of these P. falciparum isolates carried the Pfmdr-1 mutant alleles 1246Y and 86Y, respectively. Our results show high prevalence of wild type alleles N86 and D1246 in P. falciparum isolates from Lira Regional Referral Hospital, which could translate to a decreased sensitivity to artemether-lumefantrine. Continued monitoring of prevalence of single nucleotide polymorphisms is warranted to timely inform malaria treatment policies and guidelines.

Comparative genomic analysis of human infective Trypanosoma cruzi lineages with the bat-restricted subspecies T. cruzi marinkellei.

BACKGROUND: Trypanosoma cruzi marinkellei is a bat-associated parasite of the subgenus Schizotrypanum and it is regarded as a T. cruzi subspecies. Here we report a draft genome sequence of T. c. marinkellei and comparison with T. c. cruzi. Our aims were to identify unique sequences and genomic features, which may relate to their distinct niches. RESULTS: The T. c. marinkellei genome was found to be ~11% smaller than that of the human-derived parasite T. c. cruzi Sylvio X10. The genome size difference was attributed to copy number variation of coding and non-coding sequences. The sequence divergence in coding regions was ~7.5% between T. c. marinkellei and T. c. cruzi Sylvio X10. A unique acetyltransferase gene was identified in T. c. marinkellei, representing an example of a horizontal gene transfer from eukaryote to eukaryote. Six of eight examined gene families were expanded in T. c. cruzi Sylvio X10. The DGF gene family was expanded in T. c. marinkellei. T. c. cruzi Sylvio X10 contained ~1.5 fold more sequences related to VIPER and L1Tc elements. Experimental infections of mammalian cell lines indicated that T. c. marinkellei has the capacity to invade non-bat cells and undergo intracellular replication. CONCLUSIONS: Several unique sequences were identified in the comparison, including a potential subspecies-specific gene acquisition in T. c. marinkellei. The identified differences reflect the distinct evolutionary trajectories of these parasites and represent targets for functional investigation.

Shotgun sequencing analysis of Trypanosoma cruzi I Sylvio X10/1 and comparison with T. cruzi VI CL Brener.

Trypanosoma cruzi is the causative agent of Chagas disease, which affects more than 9 million people in Latin America. We have generated a draft genome sequence of the TcI strain Sylvio X10/1 and compared it to the TcVI reference strain CL Brener to identify lineage-specific features. We found virtually no differences in the core gene content of CL Brener and Sylvio X10/1 by presence/absence analysis, but 6 open reading frames from CL Brener were missing in Sylvio X10/1. Several multicopy gene families, including DGF, mucin, MASP and GP63 were found to contain substantially fewer genes in Sylvio X10/1, based on sequence read estimations. 1,861 small insertion-deletion events and 77,349 nucleotide differences, 23% of which were non-synonymous and associated with radical amino acid changes, further distinguish these two genomes. There were 336 genes indicated as under positive selection, 145 unique to T. cruzi in comparison to T. brucei and Leishmania. This study provides a framework for further comparative analyses of two major T. cruzi lineages and also highlights the need for sequencing more strains to understand fully the genomic composition of this parasite.

Characterization of a Trypanosoma cruzi acetyltransferase: cellular location, activity and structure.

Trypanosomatids are widespread parasites that cause three major tropical diseases. In trypanosomatids, as in most other organisms, acetylation is a common protein modification that is important in multiple, diverse processes. This paper describes a new member of the Trypanosoma cruzi acetyltransferase family. The gene is single copy and orthologs are also present in the other two sequenced trypanosomatids, Trypanosoma brucei and Leishmania major. This protein (TcAT-1) has the essential motifs present in members of the GCN5-related acetyltransferase (GNAT) family, as well as an additional motif also found in some enzymes from plant and animal species. The protein is evolutionarily more closely related to this group of enzymes than to histone acetyltransferases. The native protein has a cytosolic cellular location and is present in all three life-cycle stages of the parasite. The recombinant protein was shown to have autoacetylation enzymatic activity.

Comparative karyotyping as a tool for genome structure analysis of Trypanosoma cruzi.

As a part of the Trypanosoma cruzi genome project, 239 genetic markers were hybridised to PFGE separated DNA from T. cruzi, in order to determine the number and size of chromosomes and to aid the assembly of the genome sequence. We used three strains, T. cruzi IIe CL Brener (the genome project reference strain) and two T. cruzi I strains, Sylvio X10/7 and CAI/72, to perform a comparative study of their karyotypes and to determine marker linkage. A densitometry analysis of the separations estimated the total chromosome numbers to be 55 in CL Brener and 57 in the two other strains. In all, 45 markers hybridised to single chromosomal bands and 103 markers to two bands in CL Brener, while the number of markers in Sylvio X10/7 and CAI/72 were 102/68 and 61/105, respectively. Size differences between homologous chromosomes were often large, up to 1900 kb (173%). The average difference was 36% for CL Brener and 23.5% for the T. cruzi I strains. Larger differences in CL Brener are consistent with a recent hybrid origin. Forty markers distributed into 15 linkage groups were found to identify specific chromosomes or chromosomes pairs. While the same markers are generally linked in all three strains, the sizes of the chromosomes vary extensively, indicating large chromosomal rearrangements. These data provide valuable information for the finishing of the CL Brener genome sequence.