Malaria continues to cause alarming morbidity and mortality in more than 100 countries worldwide.... more Malaria continues to cause alarming morbidity and mortality in more than 100 countries worldwide. Antigens in the various life cycle stages of malaria parasites are presented to the immune system during natural infection and it is widely recognized that after repeated malaria exposure, adults develop partially protective immunity. Specific antigens of natural immunity represent among the most important targets for the development of malaria vaccines. Immunity against the transmission stages of the malaria parasite represents an important approach to reduce malaria transmission and is believed to become an important tool for gradual elimination of malaria. Development of immunity against Plasmodium falciparum sexual stages was evaluated in primary school children aged 6-16 years in Makoni district of Zimbabwe, an area of low to *
Single nucleotide polymorphisms within the cytokine genes, TNF- (-308 G/A), and IL-10 (-1082 A /... more Single nucleotide polymorphisms within the cytokine genes, TNF- (-308 G/A), and IL-10 (-1082 A /G and-819 T/C) associated with protection and susceptibility to parasitic infections were examined in samples from school aged children in the Eastern district of Zimbabwe. Whole blood specimens were obtained from 491 children between the ages of 5 – 16 years, of which 26.9% were infected with Plasmodium falciparum and 73.1% were not infected. Genotyping was carried out using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). The prevalence of TNF- genotypes GG, GA and AA associated with low, intermediate and high cytokine production was 80, 19 and 2%, respectively. Wild type alleles TNF-α-308G* predominated in both infected and uninfected individuals in the study. For IL-10 (position-819) the distribution of wild-type alleles CC*, heterozygotes and mutant carriers TT* was 64, 27 and 9%, respectively, and a similar analysis of the polymorphisms on positio...
Background: Schistosomiasis and STH are among the list of neglected tropical diseases considered ... more Background: Schistosomiasis and STH are among the list of neglected tropical diseases considered for control by the WHO. Although both diseases are endemic in Zimbabwe, no nationwide control interventions have been implemented. For this reason in 2009 the Zimbabwe Ministry of Health and Child Care included the two diseases in the 2009-2013 National Health Strategy highlighting the importance of understanding the distribution and burden of the diseases as a prerequisite for elimination interventions. It is against this background that a national survey was conducted. Methodology: A countrywide cross-sectional survey was carried out in 280 primary schools in 68 districts between September 2010 and August 2011. Schistosoma haematobium was diagnosed using the urine filtration technique. Schistosoma mansoni and STH (hookworms, Trichuris trichiura, Ascaris lumbricoides) were diagnosed using both the Kato Katz and formol ether concentration techniques. Main findings: Schistosomiasis was more prevalent country-wide (22.7%) than STH (5.5%). The prevalence of S. haematobium was 18.0% while that of S. mansoni was 7.2%. Hookworms were the most common STH with a prevalence of 3.2% followed by A. lumbricoides and T. trichiura with prevalence of 2.5% and 0.1%, respectively. The prevalence of heavy infection intensity as defined by WHO for any schistosome species was 5.8% (range 0%-18.3% in districts). Only light to moderate infection intensities were observed for STH species. The distribution of schistosomiasis and STH varied significantly between provinces, districts and schools (p,0.001). Overall, the prevalence of co-infection with schistosomiasis and STH was 1.5%. The actual co-endemicity of schistosomiasis and STH was observed in 43 (63.2%) of the 68 districts screened. Conclusion and recommendations: This study provided comprehensive baseline data on the distribution of schistosomiasis and STH that formed the basis for initiating a national control and elimination programme for these two neglected tropical diseases in Zimbabwe.
The study compared cytokine profiles of individuals from two areas with different transmission pa... more The study compared cytokine profiles of individuals from two areas with different transmission patterns for Schistosoma haematobium. One area was a high transmission (HT) while the other was a low transmission (LT) area for S. haematobium. Observations on cellular immune responses were made on stimulated peripheral blood mononuclear cells (PBMC), which were collected pre-treatment, then at 12 and 18 months post treatment. Stimulation was with schistosome worm and egg antigens and a mitogen, phaetohaemaglutinin (PHA). Observations were made on PBMC proliferation and the profiles of cytokine produced over a 5-day incubation period. The two distinct areas showed significant differences on both levels of proliferation and cytokine production for all the measured classes (IL-4, IL-5, IL-10 and IFN-gamma). PBMC from individuals from the LT area had high levels of proliferation but low cytokine production to both antigen stimulants while PBMC from individuals from the HT area showed low levels of proliferation but high cytokine production levels. Prior to treatment, individuals not excreting schistosome ova in the HT area had higher levels of proliferation to the stimulants, than the infected individuals. However, after treatment re-infected individuals showed high levels of proliferation. Before treatment, both infected and uninfected groups showed low and similar ratios, respectively, of IL-4:IFN-gamma, IL-5:IFN-gamma and IL-10:IFN-gamma, while IFN-gamma was high in the infected individuals. After treatment the non re-infected had higher levels of IL-4, IL-5 and IL-10, with the infected having high levels of IFN-gamma. Th1-like response dominated during infection with the Th2-like responses dominating post treatment and in uninfected individuals. The results indicated that the cytokine balance determines, in part, susceptibility or resistance to S. haematobium infection.
Background Chemokines have been reported to play an important role in granulomatous inflammation ... more Background Chemokines have been reported to play an important role in granulomatous inflammation during Schistosoma mansoni infection. However there is less information on their role in Schistosoma haematobium infection, or on the effect of concurrent HIV-1 infection, as a potential modifying influence. Methods To determine levels of MIP-1α/CCL3 chemokine in plasma of S. haematobium and HIV-1 co-infected and uninfected individuals in a rural black Zimbabwean community. A cohort was established of HIV-1 and schistosomiasis infection and co-infection comprising 379 participants. Outcome measures consisted of HIV-1 and schistosomiasis status and levels of MIP-1α/CCL3 in plasma at baseline and three months post treatment. An association was established between MIP-1α/CCL3 plasma levels with HIV-1 and S. haematobium infections. Results A total of 379 adults formed the established cohort comprising 76 (20%) men and 303 (80%) women. Mean age was 33.25, range 17 - 62 years. The median MIP-1...
BackgroundTrichiasis is present when one or more eyelashes touches the eye. Uncorrected, it can c... more BackgroundTrichiasis is present when one or more eyelashes touches the eye. Uncorrected, it can cause blindness. Accurate estimates of numbers affected, and their geographical distribution, help guide resource allocation.MethodsWe obtained district-level trichiasis prevalence estimates for 44 endemic and previously-endemic countries. We used (1) the most recent data for a district, if more than one estimate was available; (2) age- and sex-standardized corrections of historic estimates, where raw data were available; (3) historic estimates adjusted using a mean adjustment factor for districts where raw data were unavailable; and (4) expert assessment of available data for districts for which no prevalence estimates were available.FindingsInternally age- and sex-standardized data represented 1,355 districts and contributed 662 thousand cases (95% confidence interval [CI] 324 thousand-1.1 million) to the global total. age- and sex-standardized district-level prevalence estimates differ...
Background Chemokines have been reported to play an important role in granulomatous inflammation ... more Background Chemokines have been reported to play an important role in granulomatous inflammation during Schistosoma mansoni infection. However there is less information on their role in Schistosoma haematobium infection, or on the effect of concurrent HIV-1 infection, as a potential modifying influence. Methods To determine levels of MIP-1α/CCL3 chemokine in plasma of S. haematobium and HIV-1 co-infected and uninfected individuals in a rural black Zimbabwean community. A cohort was established of HIV-1 and schistosomiasis infection and co-infection comprising 379 participants. Outcome measures consisted of HIV-1 and schistosomiasis status and levels of MIP-1α/CCL3 in plasma at baseline and three months post treatment. An association was established between MIP-1α/CCL3 plasma levels with HIV-1 and S. haematobium infections. Results A total of 379 adults formed the established cohort comprising 76 (20%) men and 303 (80%) women. Mean age was 33.25, range 17 - 62 years. The median MIP-1α/CCL3 plasma concentration was significantly higher in S. haematobium infected compared with uninfected individuals (p = 0.029). In contrast, there was no difference in the median MIP-1α/CCL3 levels between HIV-1 positive and negative individuals (p = 0.631). MIP-1α/CCL3 concentration in plasma was significantly reduced at three months after treatment with praziquantel (p = 000). Conclusion The results of our study show that the MIP-1α/CCL3 levels were positively associated with S. haematobium egg counts at baseline but not with HIV-1 infection status. MIP-1α/CCL3 levels were significantly reduced at three months post treatment with praziquantel. We therefore conclude that MIP-1α/CCL3 is produced during infection with S haematobium. S. haematobium infection is associated with increased MIP-1α/CCL3 levels in an egg intensity-dependent manner and treatment of S. haematobium is associated with a reduction in MIP-1α/CCL3.
My current research interest include parasitic infections, immunology and vaccine targets. I have... more My current research interest include parasitic infections, immunology and vaccine targets. I have been involved in research on parasitic infections particularly for schistosomiasis, soil transmitted helminths and malaria that involved community surveillance, field diagnosis and blood sample collection for later immunological profiles determinations. We have been carrying out field trials on polyparasitism control using chemotherapy as the only alternative of current control option in the view of lack of vaccine candidates for schistosomiasis and soil transmitted helminths. As an immunologist the subject on polyparasitism has been a great challenge and more information is required to contribute towards vaccine development. Whereas, schistosomiasis has been neglected and the scourge has been rapidly increasing in resource poor settings. The neglect may have been compelled by the increasing demand for resources required for other infectious diseases like malaria, TB and HIV/AIDS. Further challenges have arisen where it has been reported by our group that schistosomiasis causes some pathology in the genital area that could predispose individuals to other infections like HIV. The search for possible methods that may prevent development of pathology has pointed to treatment as the only mainstay control of schistosomiasis. Through the activities on polyparasitism, I have utilized the opportunity for capacity building of
Background: Schistosomiasis and STH are among the list of neglected tropical diseases considered ... more Background: Schistosomiasis and STH are among the list of neglected tropical diseases considered for control by the WHO. Although both diseases are endemic in Zimbabwe, no nationwide control interventions have been implemented. For this reason in 2009 the Zimbabwe Ministry of Health and Child Care included the two diseases in the 2009–2013 National Health Strategy highlighting the importance of understanding the distribution and burden of the diseases as a prerequisite for elimination interventions. It is against this background that a national survey was conducted.
Malaria continues to cause alarming morbidity and mortality in more than 100 countries worldwide.... more Malaria continues to cause alarming morbidity and mortality in more than 100 countries worldwide. Antigens in the various life cycle stages of malaria parasites are presented to the immune system during natural infection and it is widely recognized that after repeated malaria exposure, adults develop partially protective immunity. Specific antigens of natural immunity represent among the most important targets for the development of malaria vaccines. Immunity against the transmission stages of the malaria parasite represents an important approach to reduce malaria transmission and is believed to become an important tool for gradual elimination of malaria. Development of immunity against Plasmodium falciparum sexual stages was evaluated in primary school children aged 6–16 years in Makoni district of Zimbabwe, an area of low to modest malaria transmission. Malaria infection was screened by microscopy, rapid diagnostic tests and finally using nested PCR. Plasma samples were tested for antibodies against recombinant Pfs48/45 and Pfs47 by ELISA. Corresponding serum samples were used to test for P. falciparum transmission reducing activity in Anopheles stephensi and An. gambiae mosquitoes using the membrane feeding assay. The prevalence of malaria diagnosed by rapid diagnostic test kit (Paracheck) TM was 1.7%. However , of the randomly tested blood samples, 66% were positive by nested PCR. ELISA revealed prevalence (64% positivity at 1:500 dilution, in randomly selected 66 plasma samples) of antibodies against recom-binant Pfs48/45 (mean A 405 nm = 0.53, CI = 0.46–0.60) and Pfs47 (mean A405 nm = 0.91, CI = 0.80–1.02); antigens specific to the sexual stages. The mosquito membrane feeding assay demonstrated measurable transmission reducing ability of the samples that were positive for Pfs48/45 antibodies by ELISA. Interestingly , 3 plasma samples revealed enhancement of infectivity of P. falciparum in An. stephensi mosquitoes. These studies revealed the presence of antibodies with transmission reducing immunity in school age children from a moderate transmission area of malaria, and provide further support to exploit target antigens such as Pfs48/45 for further development of a malaria transmission blocking vaccine.
Background: Chemokines have been reported to play an important role in granulomatous inflammation... more Background: Chemokines have been reported to play an important role in granulomatous inflammation during Schistosoma mansoni infection. However there is less information on their role in Schistosoma haematobium infection, or on the effect of concurrent HIV-1 infection, as a potential modifying influence.
The study compared cytokine profiles of individuals from two areas with different transmission pa... more The study compared cytokine profiles of individuals from two areas with different transmission patterns for Schistosoma haematobium. One area was a high transmission (HT) while the other was a low transmission (LT) area for S. haematobium. Observations on cellular immune responses were made on stimulated peripheral blood mononuclear cells (PBMC), which were collected pre-treatment, then at 12 and 18 months post treatment. Stimulation was with schistosome worm and egg antigens and a mitogen, phaetohaemaglutinin (PHA). Observations were made on PBMC proliferation and the profiles of cytokine produced over a 5-day incubation period. The two distinct areas showed significant differences on both levels of proliferation and cytokine production for all the measured classes (IL-4, IL-5, IL-10 and IFN-g). PBMC from individuals from the LT area had high levels of proliferation but low cytokine production to both antigen stimulants while PBMC from individuals from the HT area showed low levels of proliferation but high cytokine production levels. Prior to treatment, individuals not excreting schistosome ova in the HT area had higher levels of proliferation to the stimulants, than the infected individuals. However, after treatment re-infected individuals showed high levels of proliferation. Before treatment, both infected and uninfected groups showed low and similar ratios, respectively, of IL-4:IFN-g, IL-5:IFN-g and IL-10:IFN-g, while IFN-g was high in the infected individuals. After treatment the non re-infected had higher levels of IL-4, IL-5 and IL-10, with the infected having high levels of IFN-g. Th1-like response dominated during infection with the Th2-like responses dominating post treatment and in uninfected individuals. The results indicated that the cytokine balance determines, in part, susceptibility or resistance to S. haematobium infection.
Single nucleotide polymorphisms within the cytokine genes, TNF-(-308 G/A), and IL-10 (-1082 A /G ... more Single nucleotide polymorphisms within the cytokine genes, TNF-(-308 G/A), and IL-10 (-1082 A /G and-819 T/C) associated with protection and susceptibility to parasitic infections were examined in samples from school aged children in the Eastern district of Zimbabwe. Whole blood specimens were obtained from 491 children between the ages of 5 16 years, of which 26.9% were infected with Plasmodium falciparum and 73.1% were not infected. Genotyping was carried out using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). The prevalence of TNF-genotypes GG, GA and AA associated with low, intermediate and high cytokine production was 80, 19 and 2%, respectively. Wild type alleles TNF-308G* predominated in both infected and uninfected individuals in the study. For IL-10 (position-819) the distribution of wild-type alleles CC*, heterozygotes and mutant carriers TT* was 64, 27 and 9%, respectively, and a similar analysis of the polymorphisms on position-1082 for IL-10 revealed that most of the samples were heterozygotes (95%). There was no statistically significant difference in the frequencies of polymorphisms on TNF-(-308G/A) (X 2 = 1.820; p = 0.403), IL-10 (-1082 A/G) (X 2 = 0.242; p = 0.623) and IL-10 (-819C/T) among children infected with P. falciparum and those without infection. Finally, the high prevalence of heterozygotes would suggest moderate to high IL-10 responses in the population analyzed and that an anti-inflammatory environment dominates when faced with acute P. falciparum infection in the samples analyzed.
Malaria continues to cause alarming morbidity and mortality in more than 100 countries worldwide.... more Malaria continues to cause alarming morbidity and mortality in more than 100 countries worldwide. Antigens in the various life cycle stages of malaria parasites are presented to the immune system during natural infection and it is widely recognized that after repeated malaria exposure, adults develop partially protective immunity. Specific antigens of natural immunity represent among the most important targets for the development of malaria vaccines. Immunity against the transmission stages of the malaria parasite represents an important approach to reduce malaria transmission and is believed to become an important tool for gradual elimination of malaria. Development of immunity against Plasmodium falciparum sexual stages was evaluated in primary school children aged 6-16 years in Makoni district of Zimbabwe, an area of low to *
Single nucleotide polymorphisms within the cytokine genes, TNF- (-308 G/A), and IL-10 (-1082 A /... more Single nucleotide polymorphisms within the cytokine genes, TNF- (-308 G/A), and IL-10 (-1082 A /G and-819 T/C) associated with protection and susceptibility to parasitic infections were examined in samples from school aged children in the Eastern district of Zimbabwe. Whole blood specimens were obtained from 491 children between the ages of 5 – 16 years, of which 26.9% were infected with Plasmodium falciparum and 73.1% were not infected. Genotyping was carried out using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). The prevalence of TNF- genotypes GG, GA and AA associated with low, intermediate and high cytokine production was 80, 19 and 2%, respectively. Wild type alleles TNF-α-308G* predominated in both infected and uninfected individuals in the study. For IL-10 (position-819) the distribution of wild-type alleles CC*, heterozygotes and mutant carriers TT* was 64, 27 and 9%, respectively, and a similar analysis of the polymorphisms on positio...
Background: Schistosomiasis and STH are among the list of neglected tropical diseases considered ... more Background: Schistosomiasis and STH are among the list of neglected tropical diseases considered for control by the WHO. Although both diseases are endemic in Zimbabwe, no nationwide control interventions have been implemented. For this reason in 2009 the Zimbabwe Ministry of Health and Child Care included the two diseases in the 2009-2013 National Health Strategy highlighting the importance of understanding the distribution and burden of the diseases as a prerequisite for elimination interventions. It is against this background that a national survey was conducted. Methodology: A countrywide cross-sectional survey was carried out in 280 primary schools in 68 districts between September 2010 and August 2011. Schistosoma haematobium was diagnosed using the urine filtration technique. Schistosoma mansoni and STH (hookworms, Trichuris trichiura, Ascaris lumbricoides) were diagnosed using both the Kato Katz and formol ether concentration techniques. Main findings: Schistosomiasis was more prevalent country-wide (22.7%) than STH (5.5%). The prevalence of S. haematobium was 18.0% while that of S. mansoni was 7.2%. Hookworms were the most common STH with a prevalence of 3.2% followed by A. lumbricoides and T. trichiura with prevalence of 2.5% and 0.1%, respectively. The prevalence of heavy infection intensity as defined by WHO for any schistosome species was 5.8% (range 0%-18.3% in districts). Only light to moderate infection intensities were observed for STH species. The distribution of schistosomiasis and STH varied significantly between provinces, districts and schools (p,0.001). Overall, the prevalence of co-infection with schistosomiasis and STH was 1.5%. The actual co-endemicity of schistosomiasis and STH was observed in 43 (63.2%) of the 68 districts screened. Conclusion and recommendations: This study provided comprehensive baseline data on the distribution of schistosomiasis and STH that formed the basis for initiating a national control and elimination programme for these two neglected tropical diseases in Zimbabwe.
The study compared cytokine profiles of individuals from two areas with different transmission pa... more The study compared cytokine profiles of individuals from two areas with different transmission patterns for Schistosoma haematobium. One area was a high transmission (HT) while the other was a low transmission (LT) area for S. haematobium. Observations on cellular immune responses were made on stimulated peripheral blood mononuclear cells (PBMC), which were collected pre-treatment, then at 12 and 18 months post treatment. Stimulation was with schistosome worm and egg antigens and a mitogen, phaetohaemaglutinin (PHA). Observations were made on PBMC proliferation and the profiles of cytokine produced over a 5-day incubation period. The two distinct areas showed significant differences on both levels of proliferation and cytokine production for all the measured classes (IL-4, IL-5, IL-10 and IFN-gamma). PBMC from individuals from the LT area had high levels of proliferation but low cytokine production to both antigen stimulants while PBMC from individuals from the HT area showed low levels of proliferation but high cytokine production levels. Prior to treatment, individuals not excreting schistosome ova in the HT area had higher levels of proliferation to the stimulants, than the infected individuals. However, after treatment re-infected individuals showed high levels of proliferation. Before treatment, both infected and uninfected groups showed low and similar ratios, respectively, of IL-4:IFN-gamma, IL-5:IFN-gamma and IL-10:IFN-gamma, while IFN-gamma was high in the infected individuals. After treatment the non re-infected had higher levels of IL-4, IL-5 and IL-10, with the infected having high levels of IFN-gamma. Th1-like response dominated during infection with the Th2-like responses dominating post treatment and in uninfected individuals. The results indicated that the cytokine balance determines, in part, susceptibility or resistance to S. haematobium infection.
Background Chemokines have been reported to play an important role in granulomatous inflammation ... more Background Chemokines have been reported to play an important role in granulomatous inflammation during Schistosoma mansoni infection. However there is less information on their role in Schistosoma haematobium infection, or on the effect of concurrent HIV-1 infection, as a potential modifying influence. Methods To determine levels of MIP-1α/CCL3 chemokine in plasma of S. haematobium and HIV-1 co-infected and uninfected individuals in a rural black Zimbabwean community. A cohort was established of HIV-1 and schistosomiasis infection and co-infection comprising 379 participants. Outcome measures consisted of HIV-1 and schistosomiasis status and levels of MIP-1α/CCL3 in plasma at baseline and three months post treatment. An association was established between MIP-1α/CCL3 plasma levels with HIV-1 and S. haematobium infections. Results A total of 379 adults formed the established cohort comprising 76 (20%) men and 303 (80%) women. Mean age was 33.25, range 17 - 62 years. The median MIP-1...
BackgroundTrichiasis is present when one or more eyelashes touches the eye. Uncorrected, it can c... more BackgroundTrichiasis is present when one or more eyelashes touches the eye. Uncorrected, it can cause blindness. Accurate estimates of numbers affected, and their geographical distribution, help guide resource allocation.MethodsWe obtained district-level trichiasis prevalence estimates for 44 endemic and previously-endemic countries. We used (1) the most recent data for a district, if more than one estimate was available; (2) age- and sex-standardized corrections of historic estimates, where raw data were available; (3) historic estimates adjusted using a mean adjustment factor for districts where raw data were unavailable; and (4) expert assessment of available data for districts for which no prevalence estimates were available.FindingsInternally age- and sex-standardized data represented 1,355 districts and contributed 662 thousand cases (95% confidence interval [CI] 324 thousand-1.1 million) to the global total. age- and sex-standardized district-level prevalence estimates differ...
Background Chemokines have been reported to play an important role in granulomatous inflammation ... more Background Chemokines have been reported to play an important role in granulomatous inflammation during Schistosoma mansoni infection. However there is less information on their role in Schistosoma haematobium infection, or on the effect of concurrent HIV-1 infection, as a potential modifying influence. Methods To determine levels of MIP-1α/CCL3 chemokine in plasma of S. haematobium and HIV-1 co-infected and uninfected individuals in a rural black Zimbabwean community. A cohort was established of HIV-1 and schistosomiasis infection and co-infection comprising 379 participants. Outcome measures consisted of HIV-1 and schistosomiasis status and levels of MIP-1α/CCL3 in plasma at baseline and three months post treatment. An association was established between MIP-1α/CCL3 plasma levels with HIV-1 and S. haematobium infections. Results A total of 379 adults formed the established cohort comprising 76 (20%) men and 303 (80%) women. Mean age was 33.25, range 17 - 62 years. The median MIP-1α/CCL3 plasma concentration was significantly higher in S. haematobium infected compared with uninfected individuals (p = 0.029). In contrast, there was no difference in the median MIP-1α/CCL3 levels between HIV-1 positive and negative individuals (p = 0.631). MIP-1α/CCL3 concentration in plasma was significantly reduced at three months after treatment with praziquantel (p = 000). Conclusion The results of our study show that the MIP-1α/CCL3 levels were positively associated with S. haematobium egg counts at baseline but not with HIV-1 infection status. MIP-1α/CCL3 levels were significantly reduced at three months post treatment with praziquantel. We therefore conclude that MIP-1α/CCL3 is produced during infection with S haematobium. S. haematobium infection is associated with increased MIP-1α/CCL3 levels in an egg intensity-dependent manner and treatment of S. haematobium is associated with a reduction in MIP-1α/CCL3.
My current research interest include parasitic infections, immunology and vaccine targets. I have... more My current research interest include parasitic infections, immunology and vaccine targets. I have been involved in research on parasitic infections particularly for schistosomiasis, soil transmitted helminths and malaria that involved community surveillance, field diagnosis and blood sample collection for later immunological profiles determinations. We have been carrying out field trials on polyparasitism control using chemotherapy as the only alternative of current control option in the view of lack of vaccine candidates for schistosomiasis and soil transmitted helminths. As an immunologist the subject on polyparasitism has been a great challenge and more information is required to contribute towards vaccine development. Whereas, schistosomiasis has been neglected and the scourge has been rapidly increasing in resource poor settings. The neglect may have been compelled by the increasing demand for resources required for other infectious diseases like malaria, TB and HIV/AIDS. Further challenges have arisen where it has been reported by our group that schistosomiasis causes some pathology in the genital area that could predispose individuals to other infections like HIV. The search for possible methods that may prevent development of pathology has pointed to treatment as the only mainstay control of schistosomiasis. Through the activities on polyparasitism, I have utilized the opportunity for capacity building of
Background: Schistosomiasis and STH are among the list of neglected tropical diseases considered ... more Background: Schistosomiasis and STH are among the list of neglected tropical diseases considered for control by the WHO. Although both diseases are endemic in Zimbabwe, no nationwide control interventions have been implemented. For this reason in 2009 the Zimbabwe Ministry of Health and Child Care included the two diseases in the 2009–2013 National Health Strategy highlighting the importance of understanding the distribution and burden of the diseases as a prerequisite for elimination interventions. It is against this background that a national survey was conducted.
Malaria continues to cause alarming morbidity and mortality in more than 100 countries worldwide.... more Malaria continues to cause alarming morbidity and mortality in more than 100 countries worldwide. Antigens in the various life cycle stages of malaria parasites are presented to the immune system during natural infection and it is widely recognized that after repeated malaria exposure, adults develop partially protective immunity. Specific antigens of natural immunity represent among the most important targets for the development of malaria vaccines. Immunity against the transmission stages of the malaria parasite represents an important approach to reduce malaria transmission and is believed to become an important tool for gradual elimination of malaria. Development of immunity against Plasmodium falciparum sexual stages was evaluated in primary school children aged 6–16 years in Makoni district of Zimbabwe, an area of low to modest malaria transmission. Malaria infection was screened by microscopy, rapid diagnostic tests and finally using nested PCR. Plasma samples were tested for antibodies against recombinant Pfs48/45 and Pfs47 by ELISA. Corresponding serum samples were used to test for P. falciparum transmission reducing activity in Anopheles stephensi and An. gambiae mosquitoes using the membrane feeding assay. The prevalence of malaria diagnosed by rapid diagnostic test kit (Paracheck) TM was 1.7%. However , of the randomly tested blood samples, 66% were positive by nested PCR. ELISA revealed prevalence (64% positivity at 1:500 dilution, in randomly selected 66 plasma samples) of antibodies against recom-binant Pfs48/45 (mean A 405 nm = 0.53, CI = 0.46–0.60) and Pfs47 (mean A405 nm = 0.91, CI = 0.80–1.02); antigens specific to the sexual stages. The mosquito membrane feeding assay demonstrated measurable transmission reducing ability of the samples that were positive for Pfs48/45 antibodies by ELISA. Interestingly , 3 plasma samples revealed enhancement of infectivity of P. falciparum in An. stephensi mosquitoes. These studies revealed the presence of antibodies with transmission reducing immunity in school age children from a moderate transmission area of malaria, and provide further support to exploit target antigens such as Pfs48/45 for further development of a malaria transmission blocking vaccine.
Background: Chemokines have been reported to play an important role in granulomatous inflammation... more Background: Chemokines have been reported to play an important role in granulomatous inflammation during Schistosoma mansoni infection. However there is less information on their role in Schistosoma haematobium infection, or on the effect of concurrent HIV-1 infection, as a potential modifying influence.
The study compared cytokine profiles of individuals from two areas with different transmission pa... more The study compared cytokine profiles of individuals from two areas with different transmission patterns for Schistosoma haematobium. One area was a high transmission (HT) while the other was a low transmission (LT) area for S. haematobium. Observations on cellular immune responses were made on stimulated peripheral blood mononuclear cells (PBMC), which were collected pre-treatment, then at 12 and 18 months post treatment. Stimulation was with schistosome worm and egg antigens and a mitogen, phaetohaemaglutinin (PHA). Observations were made on PBMC proliferation and the profiles of cytokine produced over a 5-day incubation period. The two distinct areas showed significant differences on both levels of proliferation and cytokine production for all the measured classes (IL-4, IL-5, IL-10 and IFN-g). PBMC from individuals from the LT area had high levels of proliferation but low cytokine production to both antigen stimulants while PBMC from individuals from the HT area showed low levels of proliferation but high cytokine production levels. Prior to treatment, individuals not excreting schistosome ova in the HT area had higher levels of proliferation to the stimulants, than the infected individuals. However, after treatment re-infected individuals showed high levels of proliferation. Before treatment, both infected and uninfected groups showed low and similar ratios, respectively, of IL-4:IFN-g, IL-5:IFN-g and IL-10:IFN-g, while IFN-g was high in the infected individuals. After treatment the non re-infected had higher levels of IL-4, IL-5 and IL-10, with the infected having high levels of IFN-g. Th1-like response dominated during infection with the Th2-like responses dominating post treatment and in uninfected individuals. The results indicated that the cytokine balance determines, in part, susceptibility or resistance to S. haematobium infection.
Single nucleotide polymorphisms within the cytokine genes, TNF-(-308 G/A), and IL-10 (-1082 A /G ... more Single nucleotide polymorphisms within the cytokine genes, TNF-(-308 G/A), and IL-10 (-1082 A /G and-819 T/C) associated with protection and susceptibility to parasitic infections were examined in samples from school aged children in the Eastern district of Zimbabwe. Whole blood specimens were obtained from 491 children between the ages of 5 16 years, of which 26.9% were infected with Plasmodium falciparum and 73.1% were not infected. Genotyping was carried out using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). The prevalence of TNF-genotypes GG, GA and AA associated with low, intermediate and high cytokine production was 80, 19 and 2%, respectively. Wild type alleles TNF-308G* predominated in both infected and uninfected individuals in the study. For IL-10 (position-819) the distribution of wild-type alleles CC*, heterozygotes and mutant carriers TT* was 64, 27 and 9%, respectively, and a similar analysis of the polymorphisms on position-1082 for IL-10 revealed that most of the samples were heterozygotes (95%). There was no statistically significant difference in the frequencies of polymorphisms on TNF-(-308G/A) (X 2 = 1.820; p = 0.403), IL-10 (-1082 A/G) (X 2 = 0.242; p = 0.623) and IL-10 (-819C/T) among children infected with P. falciparum and those without infection. Finally, the high prevalence of heterozygotes would suggest moderate to high IL-10 responses in the population analyzed and that an anti-inflammatory environment dominates when faced with acute P. falciparum infection in the samples analyzed.
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