Fortification of Carica papaya fruit seeds to school meal snacks may aid Africa mass deworming programs: a preliminary survey.

BACKGROUND: Soil transmitted helminths (STHs) are among the world's neglected tropical diseases. Morbidity due to STHs is greatest in school-age children who typically have the highest burden of infection. In 2001, WHO passed a resolution for the use of large-scale mass drug administration (MDA) to deworm vulnerable children through school based programs. Though effective, there is concern that MDA might not be sustainable over extended periods. Additionally the current MDA strategy does not consider child malnutrition, a very common malady in resource limited countries. We report a pilot evaluation of an innovation that bundles school feeding and deworming. METHODS: We designed a maize (corn) flour fortified with grounded dried papaya (Carica papaya) seeds and used it to prepare porridge as per the usual school meal recipe Children from three primary schools from Nandi County in Kenya were randomized into three arms: One school received 300 ml papaya fortified porridge daily (papaya group), the second school received similar serving of plain porridge without the pawpaw ingredient (control group) and the third school received plain porridge and the conventional MDA approach of one time 400 mg dosage of albendazole (albendazole arm). Prior to the randomization, an initial baseline stool microscopy analysis was done to determine presence and intensity of intestinal worms. Core indicators of nutrition-height, weight and hemoglobin counts were also assessed. The children were monitored daily for two months and final stool sample analysis and clinical monitoring done at the end of the study. Baseline and follow-up data were analyzed and compared through SAS version 9.1 statistical package. RESULTS: A total of 326 children participated in the trial. The overall prevalence of Ascaris lumbricoides was 29.4% (96), Trichuris Trichura 5.2% (17) and hookworm 1 (0.3%). Papaya seed fortified porridge reduced the Ascaris lumbricoides egg count by 63.9% after the two month period (mean 209.7epg to 75.7 p < 0.002) as compared to the albendazole arm 78.8% (129.5 epg to 27.5, p value 0.006). The control group showed an increase in egg count (42.epg to 56.3) though it was not statistically significant. Hemoglobin counts in the papaya group increased from a mean of 2 g/dL (11.5 g/dL to 13.5 g/dL, p < 0.001), as compared to the albendazole arm that increased by 1 g/dL (12.8-13.9, p < 0.001). No significant change was observed in the placebo arm (13.2 to 13.1). Interestingly the papaya group showed a significant reduction of children with Tinea capitis (ringworms) (54.4 to 34%, p < 0.002) as compared to the albendazole arm that showed an increase in ringworm infestation though not statistically significant (39.7 to 64.7% p = 0.608). CONCLUSION: Papaya seed fortified porridge had a significant effect on reduction of Ascaris lumbricoides burden. It had a better nutritional outcome and effect on child fungal infections than albendazole. Its application as a routine school meal may aid current national school based nutrition and deworming programs in Africa. TRIAL REGISTRATION: This study was retrospectively registered at Clinicaltrials.gov Ref. NCT02725255 on 31st March 2016.

MEETING REPORT: UNESCO-MERCK AFRICA RESEARCH SUMMIT 2015- ACCELERATING ACCESS AND SUSTAINING INNOVATION 'FROM AFRICA FOR AFRICA'.

BACKGROUND: The Ebola virus disease outbreak of 2014 was the largest, longest and most devastating in the history of the disease. It demonstrated the social and economic impact an emerging infectious disease can have in a globalized world. Health systems in affected countries were stretched to the point of near collapse, while social relations and traditional practices were negatively impacted. Heads of African research institutions, African government representatives, leaders of global pharmaceutical companies, global infectious disease experts and close to 100 young African researchers from 25 countries; Assembled in Geneva on 19 and 20th October 2015, for the inaugural UNESCO-Merck Africa Summit sponsored by the United Nations Educational, Science and Culture Organization and Merck KGA. GOAL OF SUMMIT: The primary goal of the summit was to develop strategies to increase health research capacity in Africa, with special focus on Ebola and enhancing pandemic preparation for emerging infectious diseases. The summit was also provide a forum to showcase the research taking place in Africa, and provided platform for African researchers to network. Some of the key issues discussed included; strategies for enhancing policy frameworks to promote knowledge translation, strengthening of health systems, enhancing knowledge and data sharing, and increasing innovation in Africa. CONCLUSIONS: Summit attendees recognized that Africa still bore the heaviest burden of infectious disease, and increased commitment by African governments to fund health research, offered the best hope for developing health solutions and interventions to improve the health of Africans. Improved health in turn would enhance the productivity of Africans, further supporting the socio-economic transformation currently taking place on the continent.

Prevalence of nevirapine-associated resistance mutations after single dose prophylactic treatment among antenatal clinic attendees in north rift Kenya.

The use of single dose nevirapine to prevent mother-to-child transmission of HIV has been reported to induce drug-resistant mutations and reduce options for antiretroviral treatment for HIV-infected mothers and their children. To explore the status of nevirapine-resistant HIV genotypes in rural hospitals in the North Rift Valley Province of Kenya, samples collected 3 months after single dose nevirapine from 36 mothers and their children were analyzed. Resistance mutations were genotypically evaluated through proviral DNA amplification, cloning, and sequencing. Ten mothers (27.8%) had antiretroviral-associated resistance mutations of whom four (11.1%) had specific nevirapine (NNRTI) resistance-associated mutations. Three mothers (8.3%) transmitted the infection to their infants. This presence of nevirapine mutations in rural antenatal clinic attendees confirms the importance of integrating antiretroviral resistance monitoring as a key component in programs geared to prevention of HIV mother-to-child transmission.

CD4T lymphocyte subsets and disease manifestation in children with and without HIV born to HIV-1 infected mothers.

OBJECTIVE: To understand the natural history of HIV-1 infection in children in terms of evolution of childhood clinical manifestations versus the immune status, we prospectively studied children with and without maternally transmitted HIV-1 infection born to mothers infected with HIV-1 for two years between March 1998 and March 2000. DESIGN: A prospective cohort study. SETTING: An institutional children's home. SUBJECTS: Fifty nine children (26 males and 33 females) with and without maternally transmitted HIV-1 infection born to mothers infected with HIV-1 and adopted in institutional children home. METHODS: HIV-1 status of children under nine months was confirmed by polymerase chain reaction(PCR). ELISA for HIV-1 antibody in serum/plasma was used to confirm HIV-infection status for children aged < or = 18 months. Children were visited every three months between March and June 2000. At every visit blood was collected for total white cell count, haemoglobin and CD4+ and CD8+ T cell counts. The institutional doctor routinely examined children and treated all ailments. Clinical data were recorded. MEASURES: HIV-DNA, anti-HIV antibodies, total white blood count, total T cell counts, CD4 and CD8 T cell subset counts, frequency of childhood manifestations of infection. RESULTS: The children were aged between 4.5 and 13 years. The baseline haematological and immunological profiles (mean, mode) were: HIV-1 sero-converters (WBC 7151,7150; HB 11.6, 12.0; CD4+ 686, 795; CD8+ 2168, 1507) and HIV-1 de-seroconverters (mean, mode) were: (WBC 8386, 7150; HB 11.7, 12.8; CD4+ 735, 795; CD8+ 2168, 1507). The commonest causes of illnesses among the HIV-1 children were URTI (85.3%), TB(56.1 %), pneumonia (56.2%), tonsillitis (34.1%), parotiditis (28%) and acute otitis media (25%). The distribution of clinical manifestations was similar between the two categories of children, except URTI, whose prevalence was significantly increased among HIV-1 infected children (p-value=0.006). Among the HIV-1 infected children, only TB, parotiditis, and acute otitis media (AOM) were significantly associated with decreased CD4+ T cell count (p<0.05) resulting from HIV infection. CONCLUSIONS: HIV infection in children predisposes them to common childhood infections that can be used as markers of immune decline. TB, AOM, URTI may be early indicators of suspicion that would enable selective screening for HIV infection in children.

Maternal immune responses and risk of infant infection with HIV-1 after a short course Zidovudine in a cohort of HIV-1 infected pregnant women in rural Kenya.

OBJECTIVE: To investigate the effects of short-course nucleoside reverse transcriptase inhibitor (Zidovudine, ZDW/AZT) on maternal immune responses and risk of infant infection with HIV-1 among rural-based mothers in western Kenya. DESIGN: A prospective cohort study involving HIV-1 seropositive pregnant mothers and their infants. SUBJECTS: One hundred and seven HIV-1 seropositive asymptomatic pregnant women and their infants. METHODS: After informed consent, the women were enrolled at gestation age between 16-24 weeks. For cultural and economic reasons, all mothers were allowed to breast feed their infants. Short-course antepartum regime of AZT was administered to all mothers starting at 36 weeks gestation until start of labour. Maternal absolute CD4+ T cell subset assays were performed before 3rd trimester (about 36 weeks gestation) and after a 4-week therapy of AZT (at least one month post-nuptially). Infant HIV-1 status was determined by HIV-1 DNA polymerase chain reaction (PCR) on samples sequentially taken at 1, 2, 3, 4, 6 and 9 months and confirmed by serology at 18 months of age. INTERVENTIONS: Antepartum short-course orally administered AZT: 300mg twice-daily starting at 36 weeks gestation until start of labour, 300mg at labour onset and 300mg every three hours during labour until delivery. MAIN OUTCOME MEASURES: Maternal CD4+ T cell counts before and after AZT treatment. Determination of infant HIV-1 infection status. RESULTS: Among 107 women sampled, only 59 received full dose of AZT and thus qualified for present analysis. Of these, 12 infected their children with HIV, while 47 did not. Comparison of CD4+ T cells before and after AZT treatment scored a significant rise in all mothers (P = 0.01). This increase in CD4+ T cells was not significant among mothers who infected their infants with HIV-1 (P = 0.474). However, a significant rise in CD4+ T cells following AZT therapy was observed only in mothers who did not transmit HIV-1 to their infants (P=0.014). CONCLUSION: These data suggest that a rise in the CD4+ T cell counts following short AZT regimen, now widely in use in resource-weak countries, may be evidence of the active suppression of the replication of HIV. However, further studies to examine the multi-factorial effect of CD4+ lymphocytes and pregnancy on MTCT of HIV need to be carried out to help fully explain the effect of AZT on immune response and whether the CD4+T cell count can be used as a true test of immunological normalisation during antiretroviral therapy.

Serological investigation of HIV-1 variant subtype strains in transmission in Nairobi.

In a bid to determine the HIV-1 subtype variants in transmission in Nairobi and its possible association with clinical status, we screened 207 confirmed HIV-1 positive patients visiting HIV/AIDS laboratory at the Virus Research Centre in Nairobi between January and March 1994. We used a selfmade ELISA obtained from an established panel of HIV-1 V3 loop peptides (ANRS, France) and derived from seven isolates: MN, HXB2, SC, Z6, Z2, ELI and CDC4. Test samples were obtained from 95 blood donors and medical examination attendees, 57 patients with chronic diarrhoea, 31 confirmed pulmonary tuberculosis, 16 with pneumonia and 12 herpes zoster. Out of the total, 21.5% had antibodies against the MN strain, 19.1% had against the Z2 strain while reaction against the HXB2 strain was observed in 17.2%. SC, CDC4, Z6 and ELI had prevalences of 11.5%, 6.2%, 5.3% and 3.8% respectively. Fifteen per cent of the tested sera showed no reaction to any of the used peptides. Strong and significant associations were observed between the total number of strains a sample react to and the clinical state. We infer that both the North American consensus strains (MN and HXB2) and the African isolates (Z2 and Z6) are predominant in Nairobi. The correlation between antibody reactivity and clinical state is an interesting observation that necessitates an expanded study and, the use of strain specific peptides maybe a sensitive and easier method for use for molecular epidemiological purposes.

PIP: During January-March 1994, in Nairobi, Kenya, the sera of pre-university students, suspected AIDS/advanced HIV-infection cases, and blood donors were screened for HIV-1 antibodies at the Virus Research Centre. All confirmed HIV-1 positive samples were categorized according to the patient's clinical status. A self-made ELISA was obtained from an established panel of HIV-1 V3 loop peptides and derived from seven isolates (MN and HXB2 [North American strains], SC, CDC4, Z2 and Z6 [African strains], and ELI). The sera of the 22 confirmed HIV-1 negative students were used as negative controls. There were 207 confirmed HIV-1 cases (95 blood donors and 112 suspected AIDS/advanced HIV-infection cases). 64 (31%) and 112 (54%) samples reacted to at least 3 strains and no more than 2 strains, respectively. The remaining 31 (15%) samples did not react to any of the 7 peptide strains. Samples with CD4 cell counts greater than 500 x 1 million reacted significantly to more peptide strains than those with CD4 counts below 200 x 1 million (88% vs. 7%). Reactivity to specific strains were 21.5% for MN, 19.1% for Z2, 17.2% for HXB2, 11.5% for SC, 6.2% for CDC 4, 5.5% for Z6, and 3.8% for ELI. Anti-HXB2 antibodies were more common in blood donors than suspected AIDS/advanced HIV-infection cases (22% vs. 13%). AIDS/advanced HIV-infection cases were more likely to have no antibodies than blood donors (21% vs. 7%). A significant association existed between the number of peptide strains a patient could react to and the clinical state (p 0.01). Specifically, 77% of samples with no V3 antibodies to the seven strains had AIDS or advanced HIV infection while 55% of those which had cross reactivity with three or more strains were asymptomatic. Further research is needed to better understand this correlation. These findings suggest that use of strain specific peptides may be a sensitive and easier method for use for molecular epidemiological purposes.