Evaluation of morbidity in Schistosoma mansoni-positive primary and secondary school children after four years of mass drug administration of praziquantel in western Kenya.

BACKGROUND: World Health Organization guidelines recommend preventive chemotherapy with praziquantel to control morbidity due to schistosomiasis. The primary aim of this cross-sectional study was to determine if 4 years of annual mass drug administration (MDA) in primary and secondary schools lowered potential markers of morbidity in infected children 1 year after the final MDA compared to infected children prior to initial MDA intervention. METHODS: Between 2012 and 2016 all students in two primary and three secondary schools within three kilometers of Lake Victoria in western Kenya received annual mass praziquantel administration. To evaluate potential changes in morbidity we measured height, weight, mid-upper arm circumference, hemoglobin levels, abdominal ultrasound, and quality of life in children in these schools. This study compared two cross-sectional samples of Schistosoma mansoni egg-positive children: one at baseline and one at year five, 1 year after the fourth annual MDA. Data were analyzed for all ages (6-18 years old) and stratified by primary (6-12 years old) and secondary (12-18 years old) school groups. RESULTS: The prevalence of multiple potential morbidity markers did not differ significantly between the egg-positive participants at baseline and those at 5 years by Mann Whitney nonparametric analysis and Fisher's exact test for continuous and categorical data, respectively. There was a small but significantly higher score in school-related quality of life assessment by year five compared to baseline by Mann Whitney analysis (P = 0.048) in 13-18 year olds where malaria-negative. However, anemia was not positively impacted by four annual rounds of MDA, but registered a significant negative outcome. CONCLUSIONS: We did not detect differences in morbidity markers measured in a population of those infected or re-infected after multiple MDA. This could have been due to their relative insensitivity or a failure of MDA to prevent morbidity among those who remain infected. High malaria transmission in this area and/or a lack of suitable methods to measure the more subtle functional morbidities caused by schistosomiasis could be a factor. Further research is needed to identify and develop well-defined, easily quantifiable S. mansoni morbidity markers for this age group.

Young Adults in Endemic Areas: An Untreated Group in Need of School-Based Preventive Chemotherapy for Schistosomiasis Control and Elimination.

Parasitologic surveys of young adults in college and university settings are not commonly done, even in areas known to be endemic for schistosomiasis and soil-transmitted helminths. We have done a survey of 291 students and staff at the Kisumu National Polytechnic in Kisumu, Kenya, using the stool microscopy Kato-Katz (KK) method and the urine point-of-care circulating cathodic antigen (POC-CCA) test. Based on three stools/two KK slides each, in the 208 participants for whom three consecutive stools were obtained, Schistosoma mansoni prevalence was 17.8%. When all 291 individuals were analyzed based on the first stool, as done by the national neglected tropical disease (NTD) program, and one urine POC-CCA assay (n = 276), the prevalence was 13.7% by KK and 23.2% by POC-CCA. Based on three stools, 2.5% of 208 participants had heavy S. mansoni infections (≥400 eggs/gram feces), with heavy S. mansoni infections making up 13.5% of the S. mansoni cases. The prevalence of the soil-transmitted helminths (STH: Ascaris lumbricoides, Trichuris trichiura and hookworm) by three stools was 1.4%, 3.1%, and 4.1%, respectively, and by the first stool was 1.4%, 2.4% and 1.4%, respectively. This prevalence and intensity of infection with S. mansoni in a college setting warrants mass drug administration with praziquantel. This population of young adults is 'in school' and is both approachable and worthy of inclusion in national schistosomiasis control and elimination programs.

Impact of Mothers' Schistosomiasis Status During Gestation on Children's IgG Antibody Responses to Routine Vaccines 2 Years Later and Anti-Schistosome and Anti-Malarial Responses by Neonates in Western Kenya.

The potential consequences of parasitic infections on a person's immune responsiveness to unrelated antigens are often conjectured upon in relationship to allergic responses and autoimmune diseases. These considerations sometimes extend to whether parasitic infection of pregnant women can influence the outcomes of responses by their offspring to the immunizations administered during national Expanded Programs of Immunization. To provide additional data to these discussions, we have enrolled 99 close-to-term pregnant women in western Kenya and determined their Schistosoma mansoni and Plasmodium falciparum infection status. At 2 years of age, when the initial immunization schedule was complete, we determined their children's IgG antibody levels to tetanus toxoid, diphtheria toxoid, and measles nucleoprotein (N-protein) antigens using a multiplex assay. We also monitored antibody responses during the children's first 2 years of life to P. falciparum MSP119 (PfMSP119), S. mansoni Soluble Egg Antigen (SEA), Ascaris suum hemoglobin (AsHb), and Strongyloides stercoralis (SsNIE). Mothers' infections with either P. falciparum or S. mansoni had no impact on the level of antibody responses of their offspring or the proportion of offspring that developed protective levels of antibodies to either tetanus or diphtheria antigens at 2 years of age. However, children born of S. mansoni-positive mothers and immunized for measles at 9 months of age had significantly lower levels of anti-measles N-protein antibodies when they were 2 years old (p = 0.007) and a lower proportion of these children (62.5 vs. 90.2%, OR = 0.18, 95% CI = 0.04-0.68, p = 0.011) were considered positive for measles N-protein antibodies. Decreased levels of measles antibodies may render these children more susceptible to measles infection than children whose mothers did not have schistosomiasis. None of the children demonstrated responses to AsHb or SsNIE during the study period. Anti-SEA and anti-PfMSP119 responses suggested that 6 and 70% of the children acquired schistosomes and falciparum malaria, respectively, during the first 2 years of life.

Functional Studies of T Regulatory Lymphocytes in Human Schistosomiasis in Western Kenya.

Immunoregulation is considered a common feature of Schistosoma mansoni infections, and elevated levels of T regulatory (Treg) lymphocytes have been reported during chronic human schistosomiasis. We now report that the removal of Treg (CD4+/CD25hi/CD127low lymphocytes) from peripheral blood mononuclear cells (PBMCs) of S. mansoni-infected individuals leads to increased levels of phytohemagglutinin (PHA)-stimulated interferon gamma (IFNγ) production and decreased interleukin-10 (IL-10) responses. Exposure to schistosome antigens did not result in measurable IFNγ by either PBMC or Treg-depleted populations. Interleukin-10 responses to soluble egg antigens (SEA) by PBMC were unchanged by Treg depletion, but the depletion of Treg greatly decreased IL-10 production to soluble worm antigenic preparation (SWAP). Proliferative responses to PHA increased upon Treg removal, but responses to SEA or SWAP did not, unless only initially low responders were evaluated. Addition of anti-IL-10 increased PBMC proliferative responses to either SEA or SWAP, but did not alter responses by Treg-depleted cells. Blockade by anti-transforming growth factor-beta (TGF-ß) increased SEA but not SWAP proliferative responses by PBMC, whereas anti-TGF-ß increased both SEA- and SWAP-stimulated responses by Treg-depleted cultures. Addition of both anti-IL-10 and anti-TGF-ß to PBMC or Treg-depleted populations increased proliferation of both populations to either SEA or SWAP. These studies demonstrate that Treg appear to produce much of the antigen-stimulated IL-10, but other cell types or subsets of Treg may produce much of the TGF-ß. The elevated levels of Treg seen in chronic schistosomiasis appear functional and involve IL-10 and TGF-ß in antigen-specific immunoregulation perhaps leading to regulation of immunopathology and/or possibly decreased immunoprotective responses.

Impact of Four Years of Annual Mass Drug Administration on Prevalence and Intensity of Schistosomiasis among Primary and High School Children in Western Kenya: A Repeated Cross-Sectional Study.

Schistosomiasis remains a major public health problem in Kenya. The World Health Organization recommends preventive chemotherapy with praziquantel (PZQ) to control morbidity due to schistosomiasis. Morbidity is considered linked to intensity of infection, which along with prevalence is used to determine the frequency of mass drug administration (MDA) to school-age children. We determined the impact of annual school-based MDA on children across all primary and high school years using a repeated cross-sectional study design in five schools near Lake Victoria in western Kenya, an area endemic for Schistosoma mansoni. At baseline and for the following four consecutive years, between 897 and 1,440 school children in Grades 1-12 were enrolled and evaluated by Kato-Katz for S. mansoni and soil-transmitted helminths (STH), followed by annual MDA with PZQ and albendazole. Four annual rounds of MDA with PZQ were associated with reduced S. mansoni prevalence in all school children (44.7-14.0%; P < 0.001) and mean intensity of infection by 91% (90.4 to 8.1 eggs per gram [epg] of stool; P < 0.001). Prevalence of high-intensity infection (≥ 400 epg) decreased from 6.8% at baseline to 0.3% by the end of the study. Soil-transmitted helminth infections, already low at baseline, also decreased significantly over the years. In this high prevalence area, annual school-based MDA with high coverage across all Grades (1-12) resulted in rapid and progressive declines in overall prevalence and intensity of infection. This decrease was dramatic in regard to heavy infections in older school-attending children.

Schistosoma mansoni Infection Can Jeopardize the Duration of Protective Levels of Antibody Responses to Immunizations against Hepatitis B and Tetanus Toxoid.

BACKGROUND: Schistosomiasis is a disease of major public health importance in sub-Saharan Africa. Immunoregulation begins early in schistosome infection and is characterized by hyporesponsiveness to parasite and bystander antigens, suggesting that a schistosome infection at the time of immunization could negatively impact the induction of protective vaccine responses. This study examined whether having a Schistosoma mansoni infection at the time of immunization with hepatitis B and tetanus toxoid (TT) vaccines impacts an individual's ability to achieve and maintain protective antibody levels against hepatitis B surface antigen or TT. METHODS: Adults were recruited from Kisumu Polytechnic College in Western Kenya. At enrollment, participants were screened for schistosomiasis and soil transmitted helminths (STHs) and assigned to groups based on helminth status. The vaccines were then administered and helminth infections treated a week after the first hepatitis B boost. Over an 8 month period, 3 blood specimens were obtained for the evaluation of humoral and cytokine responses to the vaccine antigens and for immunophenotyping. RESULTS: 146 individuals were available for final analysis and 26% were S. mansoni positive (Sm+). Schistosomiasis did not impede the generation of initial minimum protective antibody levels to either hepatitis B or TT vaccines. However, median hepatitis B surface antibody levels were significantly lower in the Sm+ group after the first boost and remained lower, but not significantly lower, following praziquantel (PZQ) treatment and final boost. In addition, 8 months following TT boost and 7 months following PZQ treatment, Sm+ individuals were more likely to have anti-TT antibody levels fall below levels considered optimal for long term protection. IL-5 levels in response to in vitro TT stimulation of whole blood were significantly higher in the Sm+ group at the 8 month time period as well. CONCLUSIONS: Individuals with schistosomiasis at the start the immunizations were capable of responding appropriately to the vaccines as measured by antibody responses. However, they may be at risk of a more rapid decline in antibody levels over time, suggesting that treating schistosome infections with praziquantel before immunizations could be beneficial. The timing of the treatment as well as its full impact on the maintenance of antibodies against vaccine antigens remains to be elucidated.

Serum adiponectin in HIV-1 and hepatitis C virus mono- and co-infected Kenyan injection drug users.

Adiponectin is an important marker of anthropometric profiles of adipose tissue. However, association of adiponectin and adiposity in HIV mono- and co-infected and hepatitis (HCV) injection drug users (IDUs) has not been elucidated. Therefore, the relationship of total adiponectin levels with anthropometric indices of adiposity was examined in HIV mono-infected (anti-retroviral treatment, ART-naive, n=16 and -experienced, n=34); HCV mono-infected, n=36; HIV and HCV co-infected (ART-naive, n=5 and -experienced, n=13); uninfected, n=19 IDUs; and healthy controls, n=16 from coastal Kenya. Anthropometric indices of adiposity were recorded and total circulating adiponectin levels were measured in serum samples using enzyme-linked immunosorbent assay. Adiponectin levels differed significantly amongst the study groups (P<0.0001). Post-hoc analyses revealed decreased levels in HIV mono-infected ART-naive IDUs in comparison to uninfected IDUs (P<0.05) and healthy controls (P<0.05). However, adiponectin levels were elevated in HCV mono-infected IDUs relative to HIV mono-infected ART-naive (P<0.001) and -experienced (P<0.001) as well as HIV and HCV co-infected ART-naive (P<0.05) IDUs. Furthermore, adiponectin correlated with weight (ρ=0.687; P=0.003) and BMI (ρ=0.598; P=0.014) in HIV mono-infected ART-naive IDUs; waist circumference (ρ=-0.626; P<0.0001), hip (ρ=-0.561; P=0.001) circumference, and bust-to-waist ratio (ρ=0.561; P=0.001) in HIV mono-infected ART-experienced IDUs; waist girth (ρ=0.375; P=0.024) in HCV mono-infected IDUs; and waist-to-hip ratio (ρ=-0.872; P=0.048) in HIV and HCV co-infected ART-naive IDUs. Altogether, these results suggest suppression of adiponectin production in treatment-naive HIV mono-infected IDUs and that circulating adiponectin is a useful surrogate marker of altered adiposity in treatment-naive and -experienced HIV and HCV mono- and co-infected IDUs.