Finding the missing children for TB care and prevention in Kenya.

SETTING: One hundred high TB burden facilities in nine counties in Kenya.OBJECTIVES: 1) To increase uptake of TB preventive therapy (TPT) among child contacts aged <5 years, and 2) to increase TB diagnosis in children aged <15 years presenting to health facilities for routine care.DESIGN: For objective 1, a clinic-based child contact management strategy incorporating transport/healthcare cost reimbursement, monitoring and evaluation tools, and healthcare worker education was utilized. For objective 2, community health screeners were established in pediatric outpatient departments to perform verbal screening, flagging symptomatic children for further evaluation.RESULTS: Over 15 months, identification of 8,060 individuals diagnosed with bacteriologically confirmed TB led to 2,022 child contacts. Of these, 1,848 (91%) were evaluated; 149 (8%) were diagnosed with TB disease, leaving 1,699 (92%) eligible for TPT; 1,613 (95%) initiated TPT and 1,335 (83%) completed TPT. In outpatient settings, 140,444 children were screened; 54,236 (39%) had at least two TB symptoms; 2,395 (4%) were diagnosed with TB diseaseCONCLUSION: Health system strengthening supporting a clinic-based child contact management program increased the number of children initiating TPT. Systematic screening in outpatient clinics can lead to increased TB case notifications; however, optimal screening tools and clearer diagnostic pathways for the evaluation of these children are needed.

TB training in Kenya: building capacity for care and prevention.

BACKGROUND: Devolution of healthcare services in Kenya resulted in a large number of newly recruited tuberculosis (TB) coordinators. We describe a unique collaboration between a national tuberculosis program (NTP), a local, and an international non-governmental organization to build human resource capacity in TB care and prevention. METHODS: From 2016 to 2021, the Kenya Division of National Tuberculosis, Leprosy and Lung Disease Program, Centre for Health Solutions-Kenya, and the International Union Against Tuberculosis and Lung Disease developed and conducted a series of 7-day training courses. A key focus of training was the introduction of TBData4Action, an approach involving the local use of routinely available data to strengthen decision-making and support supervision. RESULTS: Implementation outcomes included training 331 (96%) coordinators out of 344, representing all 47 counties, 37 national officers and 21 other stakeholders using the country-tailored curriculum, including hands-on group work by county teams and field practicals. Thirty-five national facilitators were identified and mentored as local faculty. Training costs were reduced by 75% compared with international alternatives. CONCLUSION: The collaboration resulted in the training of the majority of the coordinators in a standardized approach to TB care. A sustainable approach to capacity building in local data use was found feasible; the model could be adapted by other NTPs.

CONTEXTE: La décentralisation des services de santé au Kenya a conduit au recrutement d'un grand nombre de nouveaux coordinateurs TB. Nous décrivons une collaboration unique entre un programme national de lutte contre la TB (NTP), une organisation non gouvernementale locale et une organisation non gouvernementale internationale visant à renforcer les capacités humaines en matière de prévention et de soins de la TB. MÉTHODES: De 2016 à 2021, la division kényane du programme national de lutte contre la tuberculose, la lèpre et les maladies respiratoires, le Centre for Health Solutions-Kenya et l'Union internationale contre la tuberculose et les maladies respiratoires ont développé et dispensé une série de formations en 7 jours. La formation mettait l'accent sur l'introduction de l'approche TBData4Action, qui promeut une utilisation locale des données disponibles en routine afin de renforcer la prise de décision et d'épauler les activités de supervision. RÉSULTATS: Les résultats de la mise en place de cette formation comprenaient la formation de 331 (96%) coordinateurs sur 344, représentant l'ensemble des 47 pays, 37 administrateurs nationaux et 21 autres acteurs formés à l'aide du programme adapté aux besoins du pays concerné (dont travail de groupe pratique par les équipes nationales et travaux pratiques sur le terrain). Trente-cinq facilitateurs nationaux ont été identifiés et formés comme enseignants locaux. Les coûts de la formation ont été réduits de 75% par rapport aux alternatives internationales. CONCLUSION: La collaboration a permis de former la majorité des coordinateurs à l'aide d'une approche standardisée de soins de la TB. Une approche durable de renforcement des capacités en matière d'utilisation des données locales s'est avérée réalisable. Ce modèle peut être adapté à d'autres NTP.

Schistosomes of small mammals from the Lake Victoria Basin, Kenya: new species, familiar species, and implications for schistosomiasis control.

Recent schistosomiasis control efforts in sub-Saharan Africa have focused nearly exclusively on treatment of humans with praziquantel. However, the extent to which wild mammals act as reservoirs for Schistosoma mansoni and therefore as sources of renewed transmission following control efforts is poorly understood. With the objective to study the role of small mammals as reservoir hosts, 480 animals belonging to 9 rodent and 1 insectivore species were examined for infection with schistosomes in Kisumu, in the Lake Victoria Basin, Kenya. Animals were collected from 2 sites: near the lakeshore and from Nyabera Marsh draining into the lake. A total of 6.0% of the animals captured, including 5 murid rodent species and 1 species of shrew (Crocidura olivieri) were infected with schistosomes. Four schistosome species were recovered and identified using cox1 DNA barcoding: S. mansoni, S. bovis, S. rodhaini and S. kisumuensis, the latter of which was recently described from Nyabera Marsh. Schistosoma mansoni and S. rodhaini were found infecting the same host individual (Lophuromys flavopunctatus), suggesting that this host species could be responsible for the production of hybrid schistosomes found in the area. Although the prevalence of S. mansoni infection in these reservoir populations was low (1.5%), given their potentially vast population size, their impact on transmission needs further study. Reservoir hosts could perpetuate snail infections and favour renewed transmission to humans once control programmes have ceased.

Schistosoma kisumuensis n. sp. (Digenea: Schistosomatidae) from murid rodents in the Lake Victoria Basin, Kenya and its phylogenetic position within the S. haematobium species group.

Schistosoma kisumuensis n. sp. is described based on 6 adult males and 2 adult females collected from the circulatory system of 3 murid rodent species, Pelomys isseli, Mastomys natalensis, and Dasymys incomtus. Specimens were collected from a single location, Nyabera Swamp, in Kisumu, Kenya in the Lake Victoria Basin. This new species is morphologically similar to members of the S. haematobium group, currently represented by 8 species parasitizing artiodactyls and primates, including humans. Schistosoma kisumuensis differs from these species by producing relatively small Schistosoma intercalatum-like eggs (135.2 x 52.9 microm) with a relatively small length to width ratio (2.55). Comparison of approximately 3000-base-pair sequences of nuclear rDNA (partial 28S) and mtDNA (partial cox1, nad6, 12S) strongly supports the status of S. kisumuensis as a new species and as a sister species of S. intercalatum. The cox1 genetic distance between these two species (6.3%) is comparable to other pairwise comparisons within the S. haematobium group. Separation of the Congo River and Lake Victoria drainage basins is discussed as a possible factor favoring the origin of this species.

Genetic diversity and population structure of Schistosoma mansoni within human infrapopulations in Mwea, central Kenya assessed by microsatellite markers.

A recently developed high-throughput technique that allows multi-locus microsatellite analysis of individual miracidia of Schistosoma mansoni was used to assess the levels of genetic diversity and population structure in 12 infrapopulations of the parasite, each infrapopulation derived from an infected school child from the Mwea area, central Kenya. The mean number of alleles per locus was in the range 8.22-10.22, expected heterozygosity in Hardy-Weinberg equilibrium was 0.68-0.70, and pairwise F(ST) values ranged from 0.16% to 3.98% for the 12 infrapopulations. Although the genetic diversity within each infrapopulation of S. mansoni in this area was generally high, low levels of genetic structure were observed, suggestive of high levels of gene flow among infrapopulations. Private alleles were found in 8 of the 12 infrapopulation, the highest number of private alleles recorded per infrapopulation was 3. Our data suggest that the level of gene flow among infrapopulations of S. mansoni in Mwea is extremely high, thus providing opportunity for spread of rare alleles, including those that may confer character traits such as drug resistance and virulence.

Microsatellite typing reveals strong genetic structure of Schistosoma mansoni from localities in Kenya.

Genetic diversity and population structure of seven populations of Schistosoma mansoni sampled in Kenya were assessed using five microsatellite markers. The mean number of alleles per locus, expected heterozygosity in Hardy-Weinberg equilibrium and pairwise F(ST) values ranged from 5.2 to 10.7, 0.5-0.8 and 3.6-27.3%, respectively. These data reveal that S. mansoni populations in Kenyan have relatively high levels of genetic diversity and is significantly differentiated. Our data combined with information on biogeography support the hypothesis that the strong genetic structure in Kenyan schistosomes is as a result of limited gene flow and large population sizes. Resistance to anthelminthics has not been reported among the Kenyan schistosomes, we hypothesize that this is probably due to the very little gene flow among populations, thereby limiting opportunities for the spread of rare alleles that might confer resistance to the drugs.

Impact of the crayfish Procambarus clarkii on Schistosoma haematobium transmission in Kenya.

The Louisiana red swamp crayfish, Procambarus clarkii, which was introduced into east Africa in the 1950s or 1960s, has since widely dispersed. Previous work by our group has shown that P. clarkii can reduce populations of the molluscan intermediate hosts of human schistosomes through predatory and competitive interactions. Here, we investigate whether crayfish can reduce populations of Bulinus africanus and consequently, Schistosoma haematobium prevalence in school children. Children from 6 primary schools in the Machakos and Kitui Districts of Kenya were selected for study. Schools were divided into 3 experimental-control pairs. At experimental schools, crayfish were introduced into nearby aquatic habitats harboring Bulinus africanus snails and serving as S. haematobium transmission sites. Snail habitats near control schools did not receive crayfish. Six months after crayfish introduction, all infected children were treated with praziquantel. Children were then monitored quarterly for 2 years, at which time infection and reinfection rates were compared statistically between the paired schools. In one such pair, crayfish failed to establish, resulting in neither snail control nor a reduction in transmission. At the second pair of schools, the numbers of snails were decreased by the presence of crayfish, but a clear difference in infection rates in children could not be detected, primarily because drought conditions kept overall transmission rates low. At the third school pair, crayfish established well in experimental habitats, snail numbers decreased precipitously, and children at the experimental school were significantly less likely to acquire S. haematobium infections than children at the control school. Our results indicate that under certain environmental circumstances, P. clarkii exerts a significant impact on the transmission of human schistosomiasis in Kenya. Important questions remain regarding the impact of P. clarkii on Kenyan freshwater ecosystems, not the least of which is its potential to significantly influence the epidemiology of schistosomiasis in east Africa.

Predation of aquatic stages of Anopheles gambiae by the Louisiana red swamp crawfish (Procambarus clarkii).

Laboratory experiments lasting 1-3 days were conducted in 10-liter glass aquaria to evaluate the ability of the Louisiana red swamp crawfish (Procambarus clarkii [Decapoda: Cambaridae]) to consume the aquatic forms of mosquitoes. With Anopheles gambiae as the target species, significantly fewer mosquito larvae or pupae survived in the presence of either juvenile or adult crawfish, relative to conditions without crawfish, regardless of whether crawfish had alternative food or not. When alternative food was excluded, juvenile and adult crawfish had a comparable ability to consume mosquito larvae. However, when alternative food was available, adult crawfish consumed significantly fewer mosquito larvae than did juveniles. In the case of pupae, juvenile crawfish consumed significantly more mosquito pupae than did the adults when alternative food was excluded. No significant difference, relative to controls, was found in the proportion of mosquito pupae surviving when adult crawfish had alternative food. Results of the present study show that P. clarkii has the ability to consume the aquatic forms of anopheline mosquitoes and, therefore, may have an impact on populations of pathogen-transmitting mosquitoes in an area of Kenya where the crawfish has become common.

Experimental control of the schistosome-transmitting snail Biomphalaria pfeifferi by the ampullariid snail Pila ovata.

Adults of the African ampullariid snail Pila ovata were examined for their ability to control laboratory populations of the pulmonate snail Biomphalaria pfeifferi, a widespread, intermediate host of the human pathogen Schistosoma mansoni in sub-Saharan Africa. In a 6-week experiment conducted in large (100 x 60 x 60 cm) outdoor tanks containing floating macrophytes (Nymphaea caerula) and initially set up with one adult ampullariid for every three adult pulmonates, the numbers of B. pfeifferi egg masses were always about half those in similar tanks without P. ovata. Although, by week 6, the numbers of B. pfeifferi in the control tanks (without ampullariids) had increased 5-fold, from an initial mean of 30 snails/tank, there was no significant increase in the numbers of B. pfeifferi in the experimental tanks (containing ampullariids). Results of experiments conducted in indoor glass aquaria indicated that adult P. ovata rapidly attacked egg masses or neonates (< 2.5 mm shell diameter) of B. pfeifferi but had no effect on the adults. The adult ampullariids also significantly decreased cover by floating macrophytes over a 6-week period compared with that in similar but ampullariid-free aquaria. This decrease in plant cover is relevant to biological control of the schistosome vectors as macrophytes serve as food, shelter and oviposition sites for pulmonate snails. The present result indicate the ability of P. ovata to inhibit multiplication of B. pfeifferi populations, at least under laboratory conditions, both directly, through predation, and indirectly, by competition for resources. Pila ovata may therefore prove useful in the biological control of medically important, pulmonate snails.

Enhancement of eosinophil-mediated cytotoxicity to schistosomula of Schistosoma mansoni by autologous mononuclear cells from patients.

Adherent mononuclear cells (monolayer), when co-cultured with autologous peripheral blood eosinophils isolated from patients treated for Schistosoma mansoni infections, enhanced the eosinophil-mediated killing of antibody coated schistosomula. The monolayer increased the activity of the eosinophils by 225%, and was observed in 80% of the patients studied. Heat labile factors other than complement, present in immune serum, further enhanced the ability of eosinophils to kill schistosomula in the presence of the monolayer. On their own the adherent cells did not mediate obvious damage to the parasite. Eosinophils that had been pre-incubated with the monolayer (100 mins) and tested separately, killed equal numbers of schistosomula as in the co-culture assay; this excludes the possibility of concurrent schistosomula cytotoxicity by the two cell populations. The ability of the monolayer to activate eosinophils was not altered by inhibitors of protein synthesis. The monolayer was largely consistent of monocytes as demonstrated by an over 96% positive staining for non-specific esterases.

Immune responses after treatment for Schistosoma mansoni infections.

The changes in the immune responses of patients before and at 3 weeks after treatment with anti-schistosomal drugs were investigated. Lymphocyte responses to Concanavalin A and to worm antigens were inhibited after treatment, whereas responses to cercarial and egg antigens remained unchanged. Eosinophil levels were significantly elevated after treatment and were positively correlated with the increase in anti-worm antibodies (r = 0.587), and negatively associated with anti-egg antibodies (r = -0.727). Although the eosinophil-dependent cytotoxicity to schistosomula was not significantly enhanced after treatment, some increased killing was evident of half the patients (7/15). On the other hand, the ability of adherent mononuclear cells to stimulate eosinophil functions was markedly enhanced by treatment (P less than 0.001). These studies suggest that treatment may enhance some of the potentially protective host's immune mechanisms.

Eosinophilia and eosinophil helminthotoxicity in patients treated for Schistosoma mansoni infections.

The changes in eosinophil levels and in eosinophil-mediated antibody-dependent schistosomular cytotoxicity, following treatment for Schistosoma mansoni infections, have been investigated in 2 similar groups of patients aged 15-50 years. Patients in group 1 were treated with either hycanthone or oxamniquine, and those in group 2 with hycanthone or praziquantel. Eosinophil levels were significantly increased in both groups. In group 1 peripheral blood eosinophil counts rose from a mean of 175/microliters before treatment to 745/microliters 3 weeks after treatment, and in group 2 from 181/microliters to 1066/microliters. The increase in eosinophil levels was positively correlated with a rise in circulating anti-adult worm antibodies (r = -0.587, P less than 0.05), whereas a negative correlation was recorded with anti-egg antibodies (r = -0.727). Despite some enhanced eosinophil helminthotoxicity following treatment in some of the individuals in group 1 (7/15), the change overall was not significant. In group 2, in which a different standard anti-schistosomular antibody was used, the eosinophil killing capacity recorded at 3 weeks was lower than that before commencement of treatment (t = 2.89, P less than 0.01). The eosinophil stimulating activity, detected in cultured mononuclear cell supernatants (MCS) from individual patients, correlated with eosinophil levels (r = 0.582, P less than 0.02) but there was no association with eosinophil killing. MCS activity did not appear to be boosted by treatment. These studies showed that peripheral blood eosinophil counts were increased following treatment, but their ability to kill schistosome larvae is variable and may depend on the immune serum used as the source of anti-schistosomular antibody.

Molluscicidal activity of Solanum aculeatum (family: Solanaceae) berries against Biomphalaria pfeifferi, Bulinus globosus and Lymnaea natalensis.

Aqueous suspensions of powder of sun- or freeze-dried berries of the plant Solanum aculeatum (Family Solanaceae), indigenous in Kenya, were tested for molluscicidal activity against Biomphalaria pfeifferi, Bulinus globosus and Lymnaea natalensis under laboratory conditions. One hundred or 50 mg powder L-1 of sun- or freeze-dried berries killed over 60% of the test B. pfeifferi, Bul. globosus and L. natalensis. Whereas 25 mg L-1 of the sun dried material killed less than 60% of the test snails, similar concentrations of the freeze dried molluscicide produced 60-80% mortality in the snails, under similar conditions. Using L. natalensis as the target snail, it was shown that the freeze dried material was more potent than the freeze-dried berries of S. incanum, S. nigrum or leaves of Polygonum senegalensis (Family Polygonaceae), all present in Kenya, and known to possess molluscicidal properties. The powdered material retained molluscicidal activity even after several months storage at room temperature. These findings suggest that S. aculeatum is a potent plant molluscicide, and has the potential for the control of vectors of schistosomiasis and fascioliasis in Kenya.